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Describe how bacteria divide and what features enable them to do so

1) Divide rapidly (exponentially) via transverse fission (splitting apart geometrically)

2A) Actin/tubulin homologues + mitotic apparatus --> chromosome segregation after replication
2B) Cytoskeleton --> to maintain cell shape


1) Clone
2) Strain
3) Isolate
4) Serotype

1) Clone: population derived from a single cell
2) Strain: clone that is genetically different from other clones of the same species
3) Isolate: clone cultured from a patient with an infection
4) Serotype: clone characterized by specific, important surface structures recognized by the immune system


What is the function and structure of bacterial envelopes

Function: protects bacteria, virulence factor for mammalian cells, target of antibiotics

A) Plasma membrane: lipid bilayer eq to mt inner membrane, contains respiratory chain + transport proteins
B) Cell wall: stop water flow into cell --> prevent osmotic lysis; formed by peptidoglycan (inflammatory virulence factor)
C) Structures outside cell wall


1) What is the difference between Gram positive and Gram negative bacteria?
2) How are they ID-ed via Gram stain?
3) What types of bacteria cannot be Gram-stained?

1) Gram positive: peptidoglycan has 20-50 layers
Gram negative: peptidoglycan has 1-3 layers

2) Heat fix bacteria to slide --> stain with Gentian violet dye --> add iodine which complexes/mordants with the dye --> decolorize with alcohol --> counterstain with safranin --> Gram positive is purple; negative is pink

3) Two types of bacteria that cannot be Gram-stained:
A) Acid fast- contain too much lipid for dye to penetrate e.g. Mycobacterium
B) Wall-less- no cell wall e.g. Rickettsia


Compare/contrast the structure of Gram positive vs negative bacterial envelopes

Gram-positive envelopes:
-protein fibrillae/pilli --> anchored to peptidoglycan; for adhesion to cells (virulence factor)
- lipotechoic acids --> sugar polymers linked by phosphates --> structure and stability; bind to TLR to release inflammatory cytokines
-group carbohydrates (only in some)

Gram-negative envelopes:
-outer lipid bilayer membrane external to the cell wall/peptidoglycan; anchored to peptidoglycan via lipoproteins --> highly impermeable, contains endotoxin lipopolysaccharides (LPS) and porin proteins (trimeric barrel to allow passage of solutes)
-periplasm --> space between cell membranes that contains the thin peptidoglycan, carrier proteins, enzymes, etc


What is the structure and function of LPS?

Only on Gram negative bacteria (outer leaflet of outer membrane); LPS = endotoxin

contains 3 parts:
1) O-antigen: long-chain polysaccharide that defends against complement; used to distinguish varieties of bacteria and target for antibiotics
2) Core polysaccharide: units bonded via divalent cations
3) Lipid A: disaccharide + FAs --> toxic when cell lyses open --> LPS binds to TLR --> cytokine storm + hemorrhage + septicemia


Describe bacterial motion and chemotaxis via flagella

Flagella rotate counterclockwise --> drives cell in one direction
Flagella rotate clockwise --> cell tumbles but does not move directionally

Up concentration gradient of attractant --> tumbling suppressed; smooth swimming in one direction
Down concentration gradient of attractant --> tumbling and reorientation promoted


Describe the following bacterial features:
1) S-layer
2) Capsule
3) Spores

1) S-layer: protect layer of protein external to the peptidoglycan

2) Capsule: layer of polysaccharide external to the peptidoglycan --> protects from phagocytosis
Bacteria with capsules are shiny/glistening/smooth; antigenically variable and cannot be visible on Gram stain; K1 capsule disguises E.coli by resembling human cell

3) Spores: made ONLY in Gram positive rods in unfavorable, nutrient-poor conditions; inert (dont grow or divide) and resistant to boiling and disinfecting (have to use autoclave); also do not Gram stain but spore position helps ID bacterial species


Describe two modes of genetic change among bacterial populations

Bacterial populations are clonal, large, and divide rapidly --> mutations have a substantial chance of occurring

1) Spread of favorable mutations via recombination e.g. by using antibiotic
2) Acquisition of genes from unrelated source; mediated by accessory genetic element


Describe accessory genetic elements and highlight which ones are replicons:
1) plasmids
2) viruses (bacteriophage)
3) insertion sequences
4) transposons
5) pathogenicity islands

Replicons: have sites for initiation of DNA synthesis --> chromosomes, plasmids, viruses

1) Plasmids: circular dsDNA, many types and # copies; used to determine if there is common source

2) Viruses: genetic parasite that injects genome into bacteria and uses it to replicate --> lyse cell and release progeny; temperate viruses integrate genome into provirus (latent bc of repressor)

3) Insertion sequence: can move from one location to another between replicons; contain only genes for their transposition (transposase which cleave at inverted repeats)

4) Transposon: contain genes unrelated to transposition e.g. antibiotic resistance genes

5) Pathogenicity islands: large transposons from another species; contains virulence genes (50-100)

*transposition can be either replicative or cut and paste*


Explain how virulence and antibiotic resistance genes are transferred between bacterial cells through:
1) Transformation
2) Conjugation
3) Transduction

Bacterial genome = single circular DNA molecule; DNA transfer is one way, forms merozygote intermediates (complete recipient + donor fragment), and said donor fragment is unstable unless recombined

1) Transformation: donor cell lysed and fragments released, which are taken up by recipient cell; happens naturally in streptococcus, bacillus, neisseria, and haemophilus

2) Conjugation: plasmid DNA copied from F+ and then transferred to F- recipient via conjugation bridge; can also transfer xsomes but much rarer bc it breaks the xsome bridge; R-factor --> F-like plasmid with MDR genes

3) Transduction:
A) Generalized - Virus particle contains bacterial and not viral DNA --> uptake of fragment requires DNA homology
B) Specialized - bacterial gene excised with provirus --> no homology required


Describe antigenic phase variation as a means by which bacteria evade an immune response

Describe three genetic mechanisms responsible for antigenic phase variation:
1) DNA inversion
2) DNA recombination
3) polymerase stuttering

Antigenic phase variation = continual production of new versions of surface antigens --> new forms can escape the immune response and repopulate --> turns off specificity of immune system against it

1) DNA inversion: eg crossover recombination between inverted H repeats for Salmonella flagella --> make either H1 or H2

2) DNA recombination: gene for Neisseria pili has one expressed copy and many silent copies --> recombination between these two homologous types leads to new antigenic versions

3) Polymerase stuttering: Slippage leads to changes in copy number of nucleotide repeat --> IF copy number is not multiple of 3 --> cannot maintain reading frame --> outer membrane Neisseria protein not made --> these cells cannot adhere as well, but cannot be targeted by antibody


Define selective toxicity

Antibiotics target bacterial cells - and not host cells - via unique targets (e.g. cell wall) or preferential target (bacterial ribosome, DHFR--> more selective for prokaryotic vs eukaryotic)


1) susceptible
2) resistant
3) therapeutic index
4) bacteriostatic
5) bactericidal

1) Susceptible: concentration of drug can be achieved at site of infection that inhibits the organism AND is below toxicity for human cells

2) Resistant: concentration of drug required to inhibit bacterial growth exceeds that which can be achieved safely

3) Therapeutic index: toxic dose / effective dose (better if its larger)

4) Bacteriostatic: inhibits growth but doesn't kill cells --> can lead to resistance; protein synthesis inhibitors

5) Bactericidal: kills cells and reduces number of bacteria; cell wall active agents


Describe susceptibility testing and what factors influence susceptibility

1A) Dilution test with increasing drug concentration;
MIC = minimal inhibitory concentration

B) Agar test - get aliquots from test tubes and plate to see if there is growth
MBC = minimal bactericidal concentration

If MIC is within therapeutic range of drug, but MBC is not --> bacteriostatic
If MBC is within therapeutic range of drug --> bactericidal

2) Susceptibility influenced by site of infection, local factors (e.g. pH, protein concentration, anaerobic conditions)


Distinguish between therapies:
1) Prophylactic
2) Empiric
3) Definitive

1) Prophylactic: prevent patient from becoming infected e.g. prevent wound infection after surgical procedure

2) Empiric: After symptoms appear but before infecting organism is IDed --> use single broad-spectrum agent to cover all likely pathogens

3) Definitive: After infectious organism defined and susceptibility determined --> Switch to specific, narrow-spectrum agent


Why would drug combination therapy be used? What are the possible effects?

Combination therapy is the exception and not the rule

1. Reasons to use:
A) As part of empirical therapy of severe infection when causative organism is unknown e.g. fever of unknown origin
B) treatment of polymicrobial infections
C) Enhance antimicrobial activity for specific infection
D) decrease chance of resistance and reduce toxicity to host

2. Effects:
A) Synergistic - e.g. bactericidal drugs in combination
B) Additive - e.g. bactericidal drugs in combination
C) Indifferent - using two drugs is the same as using just one
D) Antagonistic - combination less effective than individuals e.g. bacteriostatic + bactericidal drugs


For the following Gram positive cocci bacteria, compare important features (Gram type, colonies, sensitivity, environment):
1) Staphylococci
2) Streptococci
3) Enterococci

1) Staphylococci: Gram positive facultative anaerobes that are arranged in clusters; distinguished from streptococci bc they are catalase positive --> colonies are large, yellow, opaque
Resistant to heat and drying, natural habitat is skin --> nosocomial pathogens (i.e. hospital outbreaks)

2) Streptococci: Gram positive aerotolerant anaerobes that are arranged in long chains; catalase negative --> colonies are small, grey, translucent
Sensitive to heat, drying, cold, starvation; natural habitat is mucous membranes (oral, respiratory, GI, GU)

3) Enterococci: used to be part of Streptococci (part of Group D Streptococci)--> Gram positive aerotolerant arranged in long chains; catalase negative
Hardier than streptococci; natural habitat is mucous membranes (GI)


1) Describe Staph aureus and how it can be IDed

2) Describe S. aureus virulence factors:
A. Cell surface
B. Cytotoxins (cytolytic exotoxins)
C. Invasins (spreading factors)
D. Superantigen toxins

1) Staph aureus: type of Staphylococci (Gram positive, catalase positive); most common human pathogen, most often in flora of anterior nares; can ID through golden colonies (with beta hemolysis), ferments mannitol (turns agar yellow), coagulative positive (Activates blood clotting factors)

2) Virulence factors:
A. Cell surface
-Capsule: antiphagocytic microcapsule
-Protein A: on cell wall, anti-opsonic by binding to Fc portions of IgG --> prevents complement activation
-Adhesins: Facilitate attachment to host cells

B. Cytotoxins - target mammalian cell membranes
-Hemolysins (e.g. alpha toxin) --> lyse RBCs
-Leukocidin --> destroys neutrophils

C. Invasins - penetration through extracellular tissue
-Lipase (e.g. beta toxin) --> damages RBCs

D. Superantigen toxins - nonspecific binding of MHC II and TCRs --> cytokine storm
-TSST (toxic shock syndrome toxin)
-Enterotoxin (food poisoning from food left out too long E.G. mayo)
-Exfoliatin (scalded skin syndrome)


For S. Aureus, describe:
1) Clinical manifestations/diseases caused
2) Treatment

1) Clinical manifestations
A. Skin and soft tissue infections - abscess + pus e.g. furuncles, carbuncles, impetigo, cellulitis
B. Infections: Bone=Osteomyelitis (S. aureus is most common cause); Joint fluid = Septic arthritis; Blood= bacteremia and septicemia
C. Pneumonia following viral infections
D. Acute endocarditis (tricuspid valve) - associated with IV drug use
E. Superantigen toxinoses - TSS (due to TSST), gastroenteritis (due to enterotoxin, acute onset with projectile vomiting), scalded skin syndrome (due to exfoliatin)

2) Treatment
-2nd generation penicillin (penicillinase-resistant beta lactam antibiotic) used to disrupt cell wall synthesis --> use nafcillin ("Naf for Staph")
-MRSA acquires resistance to all beta lactam antibiotics by altering penicillin-binding proteins (PBP)--> use vancomycin to treat


Of the coagulase negative Staphylococci (epidermidis and saprophyticus), describe:
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Treatment

I. S. epidermidis --> part of normal skin flora
1) ID: Clustered Gram positive cocci, catalase positive, coagulase negative
2) Virulence factors: produces polysaccharide cell surface slime and adheres to bioprosthetics, acts as barrier to antibiotics and immune cells
3) Clinical Manifestations: Nosocomial infections e.g. prosthetic joints, catheters, IV lines; endocarditis of artificial heart valves (S. epidermidis is most common cause)
4) Treatment: Vancomycin (resistant to penicillin)

II. S. saprophyticus - part of normal vaginal flora
1) ID: Clustered Gram positive cocci, catalase positive, coagulase negative, Novobiocin antibiotic resistance
2) Virulence factors: extracellular slime, adhere to uroepithelial cells via lipotechoic acid
3) Clinical Manifestations: UTI, cystitis in women
4) Treatment: Penicillin G


How are streptococci classified via hemolysis and Lancefield Groups?

1) Hemolysis: strep causes destruction of RBCs
-Beta hemolytic: produce proteins that cause complete RBC destruction --> see ring
-Alpha hemolytic: produce H202 to damage cell membrane --> greenish/brown discoloration of heme
-gamma hemolytic: no hemolysis

2) Lancefield: classified based on C substance (antigenic cell wall polysaccharide)
-A e.g. S. pyogenes (beta hemolytic) --> bacitracin sensitive
-B e.g. S. agalactiae (beta) --> bacitracin resistant
-D e.g. Enterococcus faecalise, S. bovis (alpha or gamma)
-None e.g. Viridans (on oral flora; alpha), S. pneumoniae (i.e. pneumococcus; alpha)


Group A Streptococci (GAS) - S. pyogenes:
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Treatment

GAS e.g. S. pyogenes --> in throat, nasopharynx
1) ID: Gram positive streptococci + catalase negative; beta hemolytic, bacitracin sensitive; capsule of hyaluronic acid but its not immunogenic (since we have HA in our collagen)

2) Virulence:
A. M protein - antiphagocytic (prevents opsonization), inhibits complement
B. Streptolysin O (SLO) - lyse RBCs; retrospective diagnosis by detecting antibodies to SLO (i.e. ASO)
C. Streptokinase - activates plasmin to dissolve clots
D. SPExotoxins - superantigen toxins (SPEs A and C) cause scarlet fever, TSS; SPE B causes necrotizing fasciitis

3) Clinical manifestations:
A. Pyogenic infection (caused by bacteria)
-pharyngitis (strep throat)
-SSTI - impetigo (honey-crusted skin infection)
-Erysipelas - demarcated, superficial cellulitis --> skin infection with raised red patches and rash (S. pyogenes is most common cause) + cellulitis
B. Exotoxin (SPE) infections
-Scarlet fever - strawberry tongue, pharyngitis, skin rash everywhere except the phase
-Toxic shock-like syndrome
-necrotizing fasciitis

4) Treatment:
-Penicillin G for strep throat
-Penicillinase-resistant penicillin (e.g. oxacillin) for skin infections


Describe the clinical sequelae of untreated infections for Group A Streptococci i.e. S. pyogenes:
1) Acute rheumatic fever
2) Glomerulonephritis

1) Acute rheumatic fever: 2-3 weeks post pharyngitis only
-Type II Hypersensitivity: molecular mimicry Ab-mediated humoral response against myosin, which resembles M protein --> mitral damage, myocarditis
-Other clinical manifestations: JONES criteria--> J=joint arthritis, O=cardiac problems, N = subcutaneous nodules, E =erythematous rash (erythema marginatum), S = Sydenham's chorea
-CAN be prevented by early treatment of strep throat with penicillin

2) Glomerulonephritis: 1-2 weeks post pharyngitis OR skin infection e.g. impetigo
- Type III Hypersensitivity: Ab-Ag complexes
- Clinical: fluid retention/hypervolemia --> facial puffiness, hematuria (Cola-colored urine)
- CANNOT be prevented by early treatment of strep throat with penicillin


Group B Streptococci (GBS) - S. agalactiae:
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Treatment

GBS - S. agalactiae --> normal flora of female reproductive tract
1) ID: Gram positive streptococci + catalase negative; beta hemolytic, bacitracin resistant; positive hippurate and CAMP tests (increasing zone of hemolysis when plated with Staph aureus, distinguishes S. agalactiae among all other streps)

2) Virulence: antiphagocytic capsule

3) Clinical: #1 cause of neonatal meningitis, sepsis; also causes pneumonia

4) Treatment: Women screened for GBS colonization at 35 weeks; mom treated prophylactically with intrapartum Penicillin G


Enterococci (E. faecalis/faecium) + Group D Streptococci (S. bovis)
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Treatment

E. faecalis + E. faecium (Enterococci) and S. bovis (GDS non-enterococci) --> part of normal GI flora
1) ID: Gram positive streptococci + catalase negative; alpha or gamma hemolytic
-Enterococci --> grow in both 40% bile salt (bile resistant) or 6.5% NaCl
-Non-enterococci (S. bovis)--> grow in 40% bile but NOT in 6.5% NaCl

2) Virulence: None to remember

3) Clinical: E. faecalis is more common, E. faecium more dangerous
-E. faecalis and E. faecium--> UTI
-S. bovis --> endocarditis, biliary tract infection, bacteremia (Associated with colon cancer!)

4) Treatment: first-line is ampicillin + gentamycin (resistant to penicillin), second-line is vancomycin; enterococci in particular are MDR incl. vancomycin resistant (VRE)--> linezolid, pristinamycin, or tigecycline


"Non-Lancefield" Group Streptococci - Viridans e.g. S. mitis
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Treatment

Viridans group - normal flora in upper respiratory tract, oral cavity e.g. S. mitis: in oral cavity

1) ID: Gram positive streptococci + catalase negative; alpha hemolytic; resistant to bile salt + optochin, 6.5% NaCl

2) Virulence: Unencapsulated; adheres to platelets by creating dextrans from glucose

3) Clinical:
-Dental caries
-Subacute endocarditis - form vegetations on artificial or damaged mitral valves; common in IV drug users who lick the syringe (Ew)

4) Treatment: Penicillin G, synergistic with aminoglycosides


"Non-Lancefield" Group Streptococci - S. pneumoniae
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Treatment

S. pneumoniae i.e. pneumococci --> in oropharynx
1) ID: Gram positive streptococci + catalase negative; lancet cells grouped in pairs; alpha hemolytic; bile soluble and sensitive to optochin (cannot grow in presence of either bile or optochin)

2) Virulence: antiphagocytic polysaccharide capsule (85+ serotypes) --> increased risk in asplenics; also has IgA protease

3) Clinical: *Most common bacterial cause of MOPS (meningitis, otitis media esp in kids, pneumonia, and sinusitis)*
-Pneumonia - lower lobes, rust-colored sputum
-Otitis media - noncapsulated, less virulent bacteria
-Meningitis -
-Sinusitis or septicemia - bacteria in the bloodstream

4) Treatment:
-Penicillin G (non-CNS)
-Cefotaxamine, Ceftriaxone (CNS antibiotic)
-PPV vaccine - antibodies against capsule for at-risk (sickle-cell or other asplenics, children, alcoholics, elderly); adult version is IgM and childrens is IgG bc conjugated to protein


Describe the overall identifying features of Gram negative cocci - Neisseria:
1) Structural features
2) Environment
3) Virulence factors
4) Pathogenesis

1) Structural: Gram negative diplococci; often seen with neutrophils upon Gram stain; culture on Thayer-Martin chocolate agar with antibiotics

2) Environment:
-oxidase positive --> aerobic
-sensitive to heat, drying
-only grow on chocolate agar or VPN agar (NOT blood agar)

3) Virulence factors:
-pili/fimbriae with many antigenic variants --> evading immune system
-IgA protease --> survival along mucosal surfaces
-iron-binding proteins (lactoferrin and transferrin)
-Opa proteins on outer membrane --> for adhesion
-LOS endotoxin (not LPS, since carb chains are shorter than in other Gram negative species)

4) Pathogenesis:
-complement deficiencies (C5-C9) --> cannot make MAC --> Neisseria
-pyogenic cocci --> infection has pus
-mechanism: adhesion via pili and Opa proteins --> bacteria internalized --> transocytosis (enter submucosal space via epithelial cell) --> hypovolemia


N. gonorrhoeae (gonococci):
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

N. gonorrhoeae - 1 strain; in mucous membranes (GU, eye, rectum, throat)
1) ID: Gram negative diplococci, oxidase positive, sensitive to normal human serum --> cannot multiple; ferments only glucose (N. meningitidis also ferments maltose)

2) Virulence factors:
-unencapsulated (N. meningitidis has capsule)
-Same features as N. meningitidis--> LOS endotoxin, pili, Opa, iron binding proteins, IgA protease

3) Clinical manifestations:
-GU tract infections - Gonorrhea: (men) urethritis, (women) cervicitis --> pelvic inflammatory disease --> infertility
-thick white pus discharge, rectal infections, polyarthritis of one knee
-ophthalmia neonatorum - pinkeye in babies within 5 days of birth; give silver nitrate
-bacteremia is rare bc cannot grow in bloodstream

4) Epidemiology: STD, many times asymptomatic but still infectious; infection increases risk of HIV

5) Treatment: gonococci penicillin resistant --> 3rd gen cephalosporin antibiotic (ceftriaxone) + macrolide (azithromycin/doxycycline) for concomitant Chlamydia; IV ceftriaxone for opthalmia neonatorum


N. meningitidis (meningococci):
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

N. meningitidis - 3 strains; in nasopharynx, transmitted via respiratory secretions
1) ID: Gram negative, oxidase positive, can grow well in bloodstream; can ferment glucose AND maltose (N. gonorrhea only ferments glucose)

2) Virulence factors:
-antiphagocytic capsule - can switch expression of serogroups via transformation
-others are same as in N. gonorrhoeae (endotoxin via LOS, IgA protease, pili, Opa, iron binding proteins)

3) Clinical:
-LOS endotoxin (envelope proteins) --> inflammatory response --> leakage of fluid from capillaries --> hypovolemia and shock
-Meningococcemia - bacteria in bloodstream --> characteristic petechial rash, fever, chill, joint pain -->
A. FMS/Waterhouse-Friderichsen Syndrome- adrenal hemorrhage --> worsens LOS-mediated septic shock + DIC (disseminated intravascular coagulation) --> death before meningitis can develop
or B. Meningitis - pus in CSF, stiff neck, vomiting, headache

4) Epidemiology: 5-10% are carriers; most commonly affected is longer lasting immunity

5) Treatment: 3rd gen cephalosporin (ceftriaxone); rifampin prophylaxis for close contacts


Describe the four mechanisms that form the genetic basis of resistance:
1. Transformation
2. Transduction
3. Conjugation
4. Transposition

1. Transformation: small pieces of DNA that encode for resistance taken up and incorporated into genome

2. Transduction: resistance genes transferred from one bacterium to another via bacteriophage virus

3. Conjugation: resistance genes transferred directly from one bacterium to another via pilus

4. Transposition: resistance genes move between plasmid and chromosome via enzymes


Describe the biochemical mechanisms of drug resistance (mostly applicable to Gram negative):
1. Decreased intracellular drug level
2. Increased inactivation of drug
3. Decreased conversion of drug to active compound
4. Increased concentration of antagonistic metabolite
5. Altered amount of target enzyme/receptor
6. Decreased affinity of receptor for drug
7. Decreased activity of required enzyme for drug effect

1. Decreased intracellular drug level
-altered porins --> Decreased drug entry
-Gram negative pumps --> increased drug efflux

2. Increased inactivation of drug
-bacteria can produce enzymes to inactivate drugs e.g. Beta lactamase --> hydrolyzes beta lactam ring of penicillins and cephalosporins
-enzymatic modification of aminoglycosides

3. Decreased conversion of drug to active compound
-seen in antimetabolite drugs which have to be activated
-arises via mutation and selection

4. Increased concentration of antagonistic metabolite
-increased production of endogenous metabolite competes with drug for binding --> leads to resistance

5. Altered amount of target enzyme/receptor
-mutation in repressor of target
resistance plasmids contain multiple copies of target gene

6. Decreased affinity of receptor for drug
-mutation in target receptor that changes conformation of drug binding site --> reduces affinity e.g. trimethoprim resistance

7. Decreased activity of required enzyme for drug effect
-deficiency in autolytic enzymes --> turns cell wall inhibitors from bacteriocidal into bacteriostatic


What are factors that contribute to drug resistance?

-genetic change via mutation or gene transfer
-drugs provide selective pressure for resistant strains to grow --> only 10% of initial population needs to be resistant to spread
-bacteriostatic drugs increase probability of mutations bc they dont kill the bacteria --> much shorter shelf-life than bacteriocidal drugs
-antimicrobial resistance more common in strains that case nosocomial infections e.g. Staph
-areas in hospitals with highest antibiotic use e.g. ICU, ER have highest incidence of drug-resistant bacteria
-patients with resistant strains more likely to have received prior antimicrobial therapy


List overal mechanism of action of each class of antibiotics and specific drugs in each:
1) Protein synthesis inhibitors
A. 30S rb subunit inhibitors
B. 50S rb subunit inhibitors

2) DNA synthesis inhibitors
A. Antifolate drugs
B. DNA gyrase/Topo IV inhibitors

1) Protein synthesis inhibitors - inhibit 70S bacterial ribosomes
A. 30S rb subunit inhibitors
-aminoglycosides e.g. streptomycin, gentamicin, neomycin
-tetracyclines e.g. tetracycline, doxycycline, tigecycline

B. 50S rb subunit inhibitors
-macrolides --> most common e.g. erythromycin, azithromycin, calrithromycin
-Other, less commonly used: lincosamide (e.g. clindamycin), streptogramin (e.g. dalfopristin), oxazolidinone (e.g. linezolid)

2) DNA synthesis inhibitors
A. Antifolate drugs - inhibit biosynthesis of purine bases and thus DNA
-sulfonamides e.g. sulfamethoxazole
-trimethoprim, usually via TMP-SMX combo e.g. Bactrim, Septra

B. DNA gyrase/Topo IV inhibitors - block DNA replication by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV
-fluoroquinolones e.g. ciprofloxacin


Protein synthesis inhibitors --> 30S inhibitors --> Aminoglycosides:
1) Spectra of antibiotic activity (bactericidal vs bacteriostatic)
2) MOA
3) Clinical uses
4) Most common adverse reactions

1) Bactericidal against aerobic Gram negative bacteria (unique among proteins synthesis inhibitors, which are mostly bacteriostatic); have post-antibiotic effect (can kill bacteria after drug has been eliminated)

2) MOA: Binds to 30S subunit of bacterial ribosome and:
A. blocks initiation of protein synthesis
B. elicits premature termination of translation
C. incorporates incorrect AA --> kills bacteria

3) Clinical uses:
A. Streptomycin - 2nd line agent for TB in combination with INH or rifampin
B. Gentamicin (less $$) and tobramycin - severe infection by resistant Gram negative bacteria, in combo with B-lactam drug for synergy/preventing resistance
C. Amikacin - for bacteria resistant to gentamicin and tobramycin
D. Neomycin and kanamycin - topical use e.g. skin (Neosporin), eye drops (Neocin) bc toxic

4) Adverse rxns:
A. Nephrotoxicity - more likely >5 days treatment, reversible when treatment finished
B. Ototoxicity - auditory (tinnitus), vestibular (vertigo/ataxia); irreversible


Protein synthesis inhibitors --> 30S inhibitors --> Tetracyclines:
1) Spectra of antibiotic activity (bactericidal vs bacteriostatic)
2) MOA
3) Clinical uses
4) Most common adverse reactions

1) Bacteriostatic for aerobic and anaerobic Gram positive and negative bacteria, also protozoa

2) MOA: binds to 30S ribosomal subunit and prevents peptide elongation at the A site; tetracycline properties similar except for pharmacokinetics

3) Clinical uses:
A. Doxycycline - longer half-life (1x day); anthrax, malaria, early stage lyme disease
B. Tigecycline - longest half-life, IV administration; severe MDR cases, community-acquired pneumonia
C. All tetracyclines - rickettial infections (e.g. typhus, Rocky Mountain), STIs (e.g. chlamydia, cervicitis), skin and soft tissue infections (e.g. community-acquired Staph, severe acne), respiratory tract infections

4) Adverse rxns:
A. GI upset - nausea, vomiting, diiarrhea
B. Bind calcium esp in kids - grey teeth, brittle bone
C. Photosensitivity
D. Liver disturbance --> contraindicated in pregnancy


Protein synthesis inhibitors --> 50S inhibitors --> Macrolides:
1) Spectra of antibiotic activity (bactericidal vs bacteriostatic)
2) MOA
3) Clinical uses
4) Most common adverse reactions

1) Bacteriostatic for aerobic Gram positive bacteria (some negative)

2) MOA: Bind to 50S ribosomal subunit and inhibit translocation step of protein synthesis; properties similar except for pharmacokinetics (azithromycin has longest half life)

3) Clinical uses:
A. Respiratory tract infections - pneumonia (S. pneumoniae, M. pneumoniae, L. pneumophila)
B. Skin and soft tissue infections - substitute for penicillin in allergic individuals with Staph infections
C. Acute otitis media
D. Streptococcal pharyngitis (Strep throat)
E. Chlamydia
F. Diptheria and pertussis (whooping cough)

4) Adverse rxns:
A. GI upset - anorexia, nausea, vomiting, diarrhea
B. Hepatotoxicity - acute cholestatic hepatitis


Protein synthesis inhibitors --> 50S inhibitors --> Others
(lincosamide, streptogramin, oxazolidinone):
1) Spectra of antibiotic activity (bactericidal vs bacteriostatic)
2) MOA
3) Clinical uses
4) Most common adverse reactions

Lincosamide e.g. clindamycin
1) Bacteriostatic for aerobic and anaerobic Gram positive bacteria
2) MOA: Binds 50S and inhibits translocation
3) Uses: Skin and soft tissue infections
4) Adverse rxns: pseudomembranous colitis caused by C. difficile, skin rashes, diarrhea

Streptogramin e.g. quinupristin/dalfopristin (IV combo)
1) Bactericidal for strep and staph, but bacteriostatic for enterococci
2) MOA: Binds 50S and inhibits translocation
3) Uses: skin infections caused by MSSA, infections caused by vancomycin-resistant E. faecium

Oxazolidinone e.g. linezolid
1) Bactericidal for strep, but bacteriostatic for staph and enterococci
2) MOA: Binds 50S and blocks initiation of translation
3) Uses: Infections caused by MDR Gram positive bacteria e.g. MRSA, VRE


DNA synthesis inhibitors --> Antifolates --> Sulfonamides (SMX):
1) Spectra of antibiotic activity (bactericidal vs bacteriostatic)
2) MOA
3) Clinical uses
4) Most common adverse reactions

1) Bacteriostatic vs Gram negative (Some positive); bactericidal in combo with DHFR inhibitor (trimethoprim)

2) MOA: PABA analog that competitively inhibits enzyme that converts PABA to dihydrofolic acid

3) Uses (usually used in combo):
A. Sulisoxazole and sulfamethoxazole - UTI
B. Sulfasalazine - IBD e.g. ulcerative colitis

4) Adverse rxns:
A. Allergic rxns e.g. fever, rashes, urticaria, photosensitivity
B. Precipitate in urine --> crystalluria, hematuria


DNA synthesis inhibitors --> Antifolates --> Trimethoprim (TMP):
1) Spectra of antibiotic activity (bactericidal vs bacteriostatic)
2) MOA
3) Clinical uses
4) Most common adverse reactions

Trimethoprim, via TMP-SMX (sulfonamide) combo
1) TMP is bacteriostatic; TMP-SMX combo is bactericidal

2) MOA: Competitive inhibitor of bacterial dihydrofolate reductase enzyme (less effective at inhibiting mammalian DHFR)

3) Uses: UTI, salmonella, shigellosis, prostatitis, pneumocystis jiroveci pneumonia, acute exacerbation of chronic bronchitis

4) Adverse rxns:
A. less than 5 days - allergic rxns w/ rash, fever, GI upset
B. more than 5 days - hematologic e.g. megaloblastic anemia, leukopenia


DNA synthesis inhibitors --> Topo inhibitor --> Fluoroquinolones (FQs):
1) Spectra of antibiotic activity (bactericidal vs bacteriostatic)
2) MOA
3) Clinical uses
4) Most common adverse reactions

1) Bactericidal vs Gram positive (DNA gyrase) and negative (topo IV) bacteria

2) MOA:
A. Inhibits bacterial topo II (DNA gyrase) --> inhibits relaxation of positive supercoiled DNA during replication
B. Inhibits bacterial topo IV --> inhibits separation of chromosomal DNA into daughter cells during cell division

3) Uses:
A. UTI - even when caused by MDR bacteria
B. Diarrhea caused by shigella, salmonella, e. coli
C. soft tissue, bone, joint infections
D. Cipro - prophylaxis/treatment of anthrax
E. Respiratory FQs (levofloxacin, gemifloxacin, moxifloxacin) - upper and lower respiratory tract infections

4) Adverse rxns: generally well tolerated
A. GI upset - nausea, vomiting, diarrhea


Compare the structures and members of the Gram negative bacilli enteropathogen groups:
1) Enterobacteriaceae
2) Vibrionacae
3) Campylobacter and Helicobacter

1) Enterobacteriaceae: short, thick rods; petrichous (uniformly distributed flagella); oxidase negative
-Salmonella, shigella, yersinia, E. coli, etc.

2) Vibrionacae: curved rods (comma-shaped), polar flagella, oxidase positive

3) Campylobacter and Helicobacter: curved rods, not closely related to #1 or 2

*other intestinal pathogens include Clostridium, viruses, and protozoa


For Enterobacteriaceae as a whole, describe:
1) Epidemiology
2) ID
3) Virulence factors
4) Treatment

1) Epidemiology: normally inhabit intestine, spread through oral-fecal transmission --> Feces, fingers, flies, food; public health concern bc cause of many epidemics

2) ID: Non-fastidious, facultative anaerobes; normal flora are coliforms (lac+ on MacConkey agar), pathogens are lac-

3) Virulence factors: endotoxins, exotoxins, pili, antigens: H (flagella), O (LPS), K (capsule) *type of illness is governed by mix of virulence factors*

4) Treatment: Gram-negative beta-lactams [ampicillin, amoxicillin], 3rd-generation cephalosporins; aminoglycosides; TMP-SMX combo, fluoroquinolones


For non-inflammatory intestinal infections, describe:
1) location
2) pathogens
3) virulence factors
4) symptoms
5) MOA

Non-inflammatory enteritis
1) Location: small intestine

2) Pathogens: Vibrio cholerae, toxigenic E. coli

3) Virulence factors: adhesins, exotoxins

4) Symptoms: watery diarrhea, no fever, no wbc in feces

5) MOA: exotoxins stimulate salt transport --> disruption of adsorption by enterocytes --> diarrhea from osmotic flow of water


Vibrio cholerae [non-inflammatory enteritis]:
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

1) Gram negative curved/comma-shaped bacilli; cultured on blood, chocolate, or MacConkey agar; acid labile (prefers alkali environments); oxidase positive; can ID via serotyping using slide agglutination

2) Virulence factors: fimbriae attachment to receptors --> secretes cholera exotoxin --> permanently activates adenyl cyclase --> activates cAMP (GS pathway) --> high Cl- transport out of cell--> osmotic flow into intestinal lumen--> watery diarrhea

3) Clinical: Cholera --> massive watery diarrhea with rice water stools, death from loss of fluid/salts

4) Epidemiology: has caused 7 epidemics in developing countries; 1-6 due to serotype O1; non-pathogenic strains are reservoir for disease-producing clones; transmitted fecal-orally due to poor sanitation

5) Treatment: standard is oral rehydration therapy

*non-cholera Vibrios are halophiles, require special TCBS medium; cause diarrhea post consumption of shellfish


Toxigenic E. Coli [Non-inflammatory enteritis]:
1) ID
2) Virulence

Distinguish between ETEC and EPEC via:
1) MOA
2) pathogenesis

Both ETEC and EPEC cause non-inflammatory enteritis --> watery diarrhea
1) ID: Gram negative bacilli; ferments lactose --> pink colonies on MacConkey's agar; catalase positive and acid labile
2) Virulence: pili/fimbriae; antiphagocytic capsule; transmission via contaiminated water

Enterotoxigenic E. coli (ETEC)
-immune to local ETEC but not elsewhere --> most common cause of traveler's diarrhea
1) MOA: adhere to intestinal mucosa via pili
2) Pathogenesis: labile toxin (resembles cholera toxin) --> increases cAMP; stable toxin- increases cGMP

Enteropathic E. coli (EPEC)
1) MOA: adhere to surface of intestinal cells via pili and other adhesion proteins
2) Pathogenesis: Bacteria secreted into cytosol via Type III secretion--> alter the cytoskeleton --> become cupped in pedestals of membrane--> brush border disappears --> maladsorption


For inflammatory intestinal infections, describe:
1) location
2) pathogens
3) virulence factors
4) symptoms
5) MOA

Inflammatory enteritis
1) Location: small intestine (salmonella), colon/rectum (shigella, EHEC)

2) Pathogens: shigella, salmonella (non-typhoidal), invasive E. coli, campylobacter

3) Virulence: adhesins, cytotoxins, cell invasion

4) Symptoms: bloody diarrhea, fever, neutrophils in feces

5) MOA: bacteria invade and kill enterocytes --> neutrophils stimulate inflammation and diarrhea


Shigella [inflammatory enteritis]:
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

S. dysenteriae
1) ID: Gram negative bacilli; almost identical to E. coli; fecal blood and leukocytes; immotile; highly resistant to stomach acid i.e. acid stable and decarboxylase negative (salmonella and E. coli are sensitive i.e. acid labile and decarboxylase positive) --> fewer organisms required for infection

2) Virulence: four species defined by O-antigen; shigella exotoxin binds to 60S rb subunit and inhibits translation

3) Clinical: [Peyer's Patches] Shigella phagocytosed by M cells --> escape phagosome and use host actin cytoskeleton to create a tail and propel itself to adjacent cells --> triggers immune response via Type III secretion --> inflammatory blood diarrhea = bacillary dysentery
-S. dysenteriae strain causes hemolytic uremic syndrome (HUS) - toxin damages endothelial cells in glomerulus --> platelet aggregation --> lyses RBCs passing through capillaries --> HUS and renal failure *ESP in children*

4) Epidemiology: only in humans

5) Treatment: N/A


Invasive E. coli [inflammatory enteritis]
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

Invasive E. coli = Enterohemorrhagic E. coli (EHEC) = Shiga toxin producing E. coli (STEC)

1) ID: Gram negative bacilli; does not ferment sorbitol (unlike other E. coli)--> pale colonies on MacConkey agar

2) Virulence: 0157:H7 O-antigen serotype (part of LPS); Shiga-like toxin damages endothelial cells of capillaries in glomerulus of kidney--> platelet aggregation --> lyse RBCs that pass through capillaries --> bloody diarrhea + HUS

3) Clinical: inflammatory bloody diarrhea, hemolytic uremic syndrome (HUS) *ESP in children*; most common cause of Gram-negative sepsis

4) Epidemiology: fecal contamination of undercooked meat, water

5) Treatment: antibiotics not recommended--> increases toxin production


Non-typhoidal Salmonella [inflammatory enteritis]
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

Non-typhoidal Salmonella i.e. S. enteritidis
1) ID: Gram negative bacilli; found in all vertebrates, antigenic and biologic diversity; encapsulated, acid labile and motile

2) Virulence: facultative intracellular (can live inside/outside cells esp macrophages); invade intestinal wall and induce phagocytosis --> multiply in the phagocytic vacuole --> secrete proteins into cytosol via Type III --> induce macrophage apoptosis

3) Clinical: gastroenteritis --> vomiting, inflammatory bloody diarrhea

4) Epidemiology: infections from undercooked chickens; bacteria killed with cooking

5) Treatment: fluid/electrolyte replacement


Campylobacter jejuni [inflammatory enteritis]
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

C. jejuni
1) ID: Curved/comma-shaped Gram-negative rods; gullwing morphology on gram stain; thermophilic; oxidase-positive

2) Virulence: cytotoxin enters gut, penetrates mucosa, and enters blood stream --> bacteremia

3) Clinical: bloody diarrhea and gastroenteritis, Guillan Barre syndrome (autoimmune response --> demyelination of peripheral nerves and ascending paralysis); reactive arthritis

4) Epidemiology: fecal-oral transmission from contaminated food e.g. chicken

5) Treatment: selective medium?


Helicobacter pylori
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

H. pylori - in pylorus near stomach antrum
1) ID: Curved/comma-shaped Gram-negative rod; motile; oxidase and urease positive --> C02 production via urease breath test

2) Virulence: sits in submucosa --> produces urease --> makes environment alkaline

3) Clinical: gastritis, MALToma, peptic duodenal ulcers --> chronic infection linked to stomach cancer

4) Treatment: amoxicillin + clarithromycin + bismuth salt (Pepto bismol) + PPI


For penetrating intestinal infections, describe:
1) location
2) pathogens
3) virulence factors
4) symptoms
5) MOA

Penetrating disease
1) Location: intestine, local lymph nodes (Yersinia), systemic (typhoidal Salmonella)

2) Pathogens: Yersinia, typhoidal Salmonella

3) Virulence: adhesins, invasins

4) Symptoms: diarrhea --> Systemic febrile illness; lymphocytes and macrophages in feces

5) MOA: inhibition of phagocytes and invasion of intestinal wall


Yersinia enterocolitica [penetrating disease]
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

Y. enterocolitica
1) ID: Gram negative bacilli; humans are accidental hosts; safety pin pattern on bipolar staining

2) Virulence: antiphagocytic capsule; bacteria exit intestine and migrate to lymph nodes --> secrete Yop (outer membrane) proteins via Type III --> induce apoptosis of phagocytes

3) Clinical: bloody diarrhea; inflammation of lymph nodes; systemic effects - fever, can mimic appendicitis

4) Epidemiology: refrigerated foods (resistant to cold temperatures), puppy feces and contaminated milk products; toddlers commonly infected

5) Treatment: aminoglycosides, tetracycline


Typhoidal Salmonella [penetrating disease]
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

Typhoidal Salmonella i.e. S. typhi
1) ID: Gram negative bacilli; S. typhi unique to humans, cultured from bone marrow; encapsulated, acid labile and motile

2) Virulence: antiphagocytic capsule = Vi antigen; facultative intracellular (can survive inside/outside cells esp macrophages)

3) Clinical: penetrate intestine via M cells --> do not cause macrophage apoptosis (as with Yersinia or S. enteritidis) but spread by macrophages throughout the body --> typhoid fever --> rose-colored macules/spots on abdomen, constipation, headache, enlargement of liver and spleen

4): Epi: Typhoid Mary; chronic carriers store bacteria in gall bladder; #1 cause of osteomyelitis in patients with sickle cell disease

5) Prevention: live attenuated vaccine; treated with antibiotic e.g. fluoroquinolone (Cipro)


E. coli --> UTI [Extraintestinal infections]

another variety of E.coli cause >80% of UTI, also caused by Klebsiella and Proteus

1) ID: Gram negative bacilli; dipstick tests to detect bacterial enzymes; E. coli is catalase positive lactose fermenter (grows pink on MacConkey's agar)
2) Virulence: P=fimbriae for adhesion to UT epithelium
3) Clinical: bacteria travel up to bladder --> cystitis --> urgency, frequency, dysuria
-bacteria travel to kidney --> pyelonephritis --> fever, low back pain


E. coli K1 --> neonatal infections [Extraintestinal infections]

E. coli K1

1) ID: Gram negative bacilli; K1 serotype
2) Virulence: antiphagocytic capsule that has K antigen, cytotoxin, S fimbriae which can attach to choroid plexus in CNS, iron acquisition systems
3) Clinical: neonatal septicemia, meningitis

*can cause neonatal septicemia/meningitis ONLY if it has the K antigen on the antiphagocytic capsule*


What are the main Enterobacteriaceae pathogens that cause opportunistic and nosocomial infections?

Cause nosocomial infections - pneumonia, UTI; all MDR; all ferment lactose (only other bacteria to do this is E. coli)

1) Enterobacter - many species are MDR; motile

2) Klebsiella - encapsulated, urease positive; 3A's (Alcoholics, abcesses, aspiration); produces bloody "currant jelly" sputum; can be mistaken for TB

3) Serratia- red colonies; many species are MDR


Haemophilus influenzae [respiratory pathogen]
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

H. influenzae - mucous membrane of upper respiratory tract
1) ID: Slender Gram negative coccobacilli but pleomorphic; grows only on chocolate agar --> Requires NAD (Factor V) and hemin (Factor X)

2) Virulence: can be unencapsulated or capsulated; IgA protease, iron-binding proteins

3) Clinical: Unencapsulated --> local spread --> otitis media or cherry red epiglottitis
-Capsulated bacteria --> invade respiratory system --> pneumonia, meningitis (Type B capsule) *ESP in children* and sepsis, septic arthritis

4) Epidemiology: humans only via respiratory droplets (aerosol transmission); patients with sickle cell/without spleens are more susceptible bc spleen is responsible for getting rid of encapsulated organisms

5) Treatment/Prevention: Vaccine (2-18 mos)--> type B polysaccharide linked to diptheria toxoid; 3rd generation cephalosporin (ceftriaxone) for systemic disease; rifampin for prophylaxis in close contact


Bordetella pertussis [respiratory pathogen]
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

B. pertussis
1) ID: Gram negative coccobacilli; small colonies on blood agar; diagnose via NAAT nucleic acid test

2) Virulence: survives only briefly in environment
A. Adhesins - BrkA (outer membrane protein to resist complement), filamentous hemagglutinin (attachment protein/pili that binds ciliated epithelial cells) --> releases toxins once attached
B. Toxins
i. Tracheal toxin - IL-1 killing of ciliated epithelial cells
ii. Adenylate cyclase toxin --> rise in cAMP + macrophage apoptosis (Acts like edema factor toxin in B. anthracis)
iii. Pertussis toxin - ribosylates and inactivates Gi --> rise in cAMP and impairs leukocyte chemotaxis to C5a --> lymphocytosis (increased # lymphocytes)

3) Epi: humans only via respiratory droplets (Aerosol transmission); highly contagious

4) Clinical: Pertussis = cold-like symptoms --> paroxysmal stage: whooping cough, vomiting, cyanosis, syncope/convulsions

5) Treatment/Prevention: killed vaccine (no longer available) and acellular vaccine - rationally designed to target specific virulence factors; macrolide antibiotics


Legionella pneumophila [respiratory pathogen]
1) How they can be IDed
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

Legionella pneumophila
1) ID: Gram negative slender bacilli; highly fastidious - visualize via silver stain; requires BCYE (buffered charcoal yeast extract) agar with cysteine + iron; oxidase positive; can detect in urine antigen test (esp for serotype 1 infection)

2) Virulence: Multiplies in phagosomes of macrophages and in amoebae host

3) Clinical:
A. Pontiac fever - self-limiting fever and malaise
B. Legionnaire's (more common in smokers)- unilobar pneumonia with hyponatremia (


Brucella [zoonosis]
1) How they can be IDed
2) Source
3) Clinical manifestations
4) Treatment/Prevention

1) ID: Small Gram negative coccobacillus; highly infectious, facultative intracellular inside macrophages by preventing phagolysosome fusion; need special Brucella agar

2) Source: Reservoir is livestock; transmitted directly via contact with farm animals e.g. cow, pig (vet, butcher/ slaughterhouse worker, farmer) or indirectly via unpasteurized dairy

3) Clinical: Brucellosis --> systemic febrile illness (undulating fever, chills, anorexia); complications --> can travel and spread to spleen, liver and cause osteomyelitis

4) Treatment/prevention: testing and immunization of cattle; treat via tetracyclines (doxycycline) + RIF as adjunctive therapy


Pasteurella multocida [zoonosis]
1) How they can be IDed
2) Source
3) Clinical manifestations
4) Treatment/Prevention

Pasteurella multocida
1) ID: Small encapsulated Gram negative coccobacillus, bipolar "Safety pin" staining; culture in blood agar

2) Source: normal oral flora of domestic animals (Cats and dogs)--> animal bites

3) Clinical: soft tissue infection e.g. cellulitis; chronic infection can cause osteomyelitis

4) Treatment: Augmentin (amoxicillin + clavuronic acid)


Francisella tularensis [zoonosis]
1) How they can be IDed
2) Source
3) Clinical manifestations
4) Treatment/Prevention

Francisella tularensis
1) ID: Small Gram negative coccobacillus; one of the most infectious organisms known; facultative intracellular

2) Source: transmission from wild animals esp rabbits --> direct contact, insect vector is the dermacenter tick
-oral or pharyngeal transmission - contaminated food/water
-respiratory transmission- aerosol inhalation eg running rabbit over with lawnmower --> can be biological agent

3) Clinical: Tularemia-->
-ulceroglandular - ulcer at site of skin infection --> bacteria tunnels through lymph nodes and causes granulomas with center of caseating necrosis, spreads to other lymph nodes

4) Prevention: Avoid skin contact with sources + ticks; aminoglycoside


Yersinia pestis [zoonosis]
1) How they can be IDed
2) Source
3) Virulence factors
4) Clinical manifestations
5) Treatment/Prevention

Yersinia pestis
1) ID: Gram negative bacilli, member of Enterobacteriaceae; grows on MacConkey and blood agar; lactose negative; safety pin pattern in bipolar Wayson staining

2) Source: rodents are the reservoir - in the US its praire dogs, transmitted via flea vector; bacteria secrete coagulase enzyme that causes flea to regurgitate prior meal --> allows bacteria to enter through bite wound

3) Virulence: Yops (outer membrane proteins) via Type III secretion cause phagocyte paralysis --> prevents phagocytosis, iron binding proteins, antiphagocytic capsule

4) Clinical: Bubonic plague/Black Death -->
-"bubo" - swelling due to lymphadenopathy
-infection spreads to blood, lungs, meninges --> necrosis
-"pneumonic plague" - direct human to human transmission via respiratory droplets --> potential viral threat agent

5) Treatment: aminoglycoside (e.g. streptomycin) + tetracycline; killed vaccine is available


Pseudomonas aeruginosa [opportunistic infection]
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

Pseudomonas aeruginosa - type of Enterobacteriaceae
1) ID: Non-fastidious Gram negative rods with polar flagella; oxidase positive and does not produce acids from sugars ("non fermenting"); produces blue/green pigment and grape-like odor; obligate aerobe

2) Virulence: encapsulated, LPS + pili + extracellular polysaccharides, exotoxin A (ribosylates EF2 like the diphtheria toxin); Type III secretion

3) Clinical:
-(healthy) community acquired infections e.g. hot tub folliculitis, otitis externa
-ecthyma gangrenosum - black necrotic skin lesions
-(cystic fibrosis) chronic respiratory infection and failure
-nosocomial infections esp in burn victims, intubated patients --> #1 cause of Gram -ve nosocomial pneumonia

4) Epi: ubiquitous in environment (soil, water, biofilms, etc) esp aquatic environment; multiple forms of antibiotic resistance

5) Treatment: Anti-pseudomonas beta lactam (e.g. piperacillin) + aminoglycoside, fluoroquinolone

*Burkholderia is another Gram negative rod similar to Pseudomonas*


1) Describe the unique growth characteristics and cell wall structure of Mycobacteria

2) Which species are highly pathogenic for humans?

1) Mycobacteria:
-cannot be Gram stained bc envelope has high lipid content --> arabinogalactan, mycolic acid, and acyl lipids; has porins but does not have LPS on outer cell membrane --> resistant to heat, drying, cold
-thin, rod shaped, although some are branched; slightly curved shape
-obligate aerobe and non-motile
-acid-fast - once cells are stained they retain dye even with stringent decolorization (bc of the mycolic acid)
-slow-growing --> slow evolving infections
-virulent bacteria must grow in serpentine cords (due to presence of cord factor in the cell envelope)

2) M. tuberculosis [MTB] --> ALWAYS considered a pathogen (not part of normal flora)
M. bovis (attenuated strain of M. bovis = BCG vaccine)
M. leprae
*MTB complex includes M. bovis, M. bovis BCG, etc


Describe the pathogenesis of M. tuberculosis (MTB) including transmission and factors affecting transmission

-MTB Is human pathogen, transmitted via respiratory route (inhalation of respiratory droplets); mostly affects middle and lower lobes of lung
-transmission requires close contact --> crowded, poor living conditions

-Pathogenesis: inhalation of droplets--> bacteria reach lungs and travel to alveoli--> reside and multiply in alveolar macrophages --> cell-mediated immunity --> granulomatous inflammation at foci --> bacteria spreads to lymph nodes --> forms tubercules (granulomas with centers of caseating necrosis)--> caseous necrosis of lesions, which become calcified --> calcified lesions + hilar lymph nodes = Ghon complex

Factors affecting transmission:
-immunosusceptibility of exposed person (HIV+)

Primary TB: (1) Healed latent TB, (2) systemic infection - miliary TB, (3) Reactivation TB


Describe MTB laboratory diagnosis:
1. Specimens
2. Specimen processing
3. Direct detection
4. Cultivation
5. ID
6. Susceptibility testing

1) Specimens: respiratory, urine, stool, blood

2) Processing: specimens from non-sterile sites must be decontaminated e.g. NaOH

3) Direct detection
A. Acid fast stain: Ziehl-Neelsen carbol fuschin stain allows dye to penetrate via heat
B. Fluorochrome stain: uses fluorescent dye and is more sensitive than ZN

4) Cultivation: use Lowenstein-Jensen and Middlebrook agars + BACTEC radiation test to assess antibiotic sensitivity

5) ID: acid fast smears, nucleic acid probes via NAAT (preferred but does not replace acid fast)


Compare and contrast latent Mtb infection and active Mtb infection incl clinical signs/symptoms

*What is miliary TB?

1) Latent TB: TB infection latent in most immunocompetent people due to immunity (delayed type hypersensitivity DTH), but bacteria persist lifelong; activated macrophages form granuloma barrier around tubercle bacilli and keep them contained; no symptoms and cannot spread TB bacteria to others --> positive skin test but normal chest X ray

2) Active TB: immune system cannot keep tubercle bacilli under control or later becomes compromised (Age, HIV+) --> granulomas break down --> bacteria escape and disseminate; active TB can be progressive primary infection, reactivation, or reinfection; has symptoms and may be infectious --> has positive skin test and abnormal chest X-ray (can see calcified lesions of lung parenchyma + lymph nodes--> Ghon complex)

Clinical signs/symptoms:
-chronic low grade fever (active TB that becomes latent)
-productive cough and bloody sputum + night sweats (active TB bc of reactivation)
-cachexia (wasting) and weight loss --> due to cytokines released by active macrophages

Miliary TB - infected lymph node erodes vessel wall and bacteria spread through bloodstream to other parts of body --> looks like millet seeds on X ray
*TB can present as disease of any organ e.g. brain, bone, kidney, lung, lymph node bc bacteria can spread


What are methods of demonstrating latent TB i.e. Delayed Type IV hypersensitivity?

1. Mantoux skin testing = Type IV (Delayed-type) Hypersensitivity: inject antigenic reagent (tuberculin or PPD) and measure ring of induration after 48-72 hrs --> demonstrates prior infection but not necessarily active disease *gold standard test*

2. Interferon gamma release assay (IGRA) - another way to test for DTH; measurements of IFN-gamma from whole blood, whole blood + MTB peptides, whole blood + mitogen; use when there is low chance of patient follow-up, or if patient has been given BCG vaccine


What is the Runyon Classification system of Nontuberculous Mycobacteria (NTMs)?

NTM infections primarily from environment, not human to human transmission

Group I: Photochromogen (grow in light)
-M. kansasii, M. marinum
Group II: Scotochromogen (grow in light or dark)
-M. gordonae (most common NTM), M. xenopi (Causes COPD)
Group III: Nonphotochromogen (no pigment)
-M. avium complex (MAC)
Group IV: Rapid growing Mycobacteria


Mycobacteria leprae
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

M. leprae
1) ID: cannot be cultivated in vitro; acid-fast bacteria (bc of mycolic acid in cell wall) --> use Carbol fuschin stain

2) Virulence: spread person to person via nasal secretions; long incubation period; thrives in cold temperatures

3) Clinical: two types of leprosy
A. Tuberculoid leprosy via TH1 (cell-mediated immunity) - macrophages engulf bacteria and contain infection --> few well-demarcated, hairless lesions; screen via Lepromin skin test (Type IV hypersensitivity) --> positive result means cell mediated immune response is intact
B. Lepromatous leprosy via TH2 (humoral immunity) - "glove and stocking" neuropathy at extremities; many poorly demarcated, raised lesions on extensor surfaces, "leonine facies" - facial deformities incl. collapse of nose, loss eyebrows/lashes, nodular earlobes

4) Epidemiology: 6M cases worldwide; reservoir in USA is armadillo (aka Hansen's disease)

5) Treatment: Antibiotic therapy - may prevent neuropathy and deformity
A. Tuberculoid: Dapsone + Rifampin, 6 mos
B. Lepromatous: Clofazamine + Dapsone + Rifampin, years


Corynebacterium diphtheriae
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

C. diphtheriae
1) ID: Gram-positive club-shaped bacilli/rods in V or L shaped pairs; black colonies on Tinsdale's agar with tellurite (to inhibit other respiratory flora); nonmotile

2) Virulence: unencapsulated; AB exotoxin - B (binding) attaches to cells, A (active) enters and inactivates EF2 via ADP ribosylation--> inhibits peptide elongation and protein synthesis--> cell dies

3) Clinical: Diphtheria - inflammation of upper respiratory tract (throat and nasopharynx) with thick, grey pseudomembrane (fibrin, leukocytes, dead cells) covering inflamed, bleeding submucosa --> throat pain, lymphadenopathy ("bulls neck") fever, death from detachment and aspiration of the membrane; also heart problems and local paralysis due to demyelination of neurons in posterior pharynx

4) Epidemiology: human host; transmission via respiratory droplets; rare bc of widespread vaccination

5) Treatment: DTP vaccine contains diphtheria toxoid; also equine antitoxin or human immunoglobulin if unvaccinated person is infected


Bacteroides fragilis [Gram negative anaerobic rod]
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

B. fragilis - normal flora of colon and dental plaque; among most commonly isolated from blood cultures

1) ID: Gram negative rod; obligate anaerobe; culture on rich media; ID of specific species rarely done bc infections contain multiple species

2) Virulence: antiphagocytic capsule, LPS has no lipid A (--> no endotoxic activity), exotoxin

3) Clinical: exotoxin cleaves E-cadherin --> loosens junctions bw enterocytes --> flow of fluid into intestinal lumen --> bacteremia

4) Epi: spread from endogenous sources, infections often contain multiple species of anaerobic and facultative bacteria

5) Treatment: "To heal, use steel" --> surgical drainage and removal of necrotic tissue; antibiotics include clindamycin, penicillins, but NOT aminoglycosides


Bacillus anthracis
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

B. anthracis
1) ID: Large Gram positive rods in chains (unique among bacilli); form endospores - oval and centrally located; blood agar: large, gray, nonhemolytic, nonmotile colonies; obligate aerobe or facultative anaerobe (in macrophages)

2) Virulence: encoded by two plasmids; affects mainly macrophages
A. Antiphagocytic capsule - made of protein (poly-D glutamate), not polysaccharides
B. 3 exotoxins: Edema Factor (increases cAMP --> fluid outflow), lethal factor (cleaves MAPK --> tissue necrosis), and protective antigen (cell entry of EF and LF)

3) Clinical: death from septic shock + anthrax toxins
A. Cutaneous (95%)- black eschar (necrotic lesion surrounded by erythema)
B. Inhalation = "Wool-sorter's disease" (spores in wool)--> hemorrhagic lymphadenitis + pulmonary hemorrhage, often fatal; see widened mediastinum on Chest X-ray
C. GI - ingestion of contaminated food (B. cereus leads to food poisoning after eating reheated rice)
D. Oropharyngeal - v rare

4) Epi: enzootic disease, highly contagious - biological agent

5) Treatment: aggressive treatment essential; use fluroquinolone (Cipro) + doxycycline; erythromycin for cutaneous anthrax; multidrug for inhaled anthrax


Listeria monocytogenes
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

Listeria monocytogenes
1) ID: Slender Gram positive rod; motile --> "umbrella tumbling motility" through flagella when outside the cell, actin rocket when inside the cell (facultative anaerobe); beta hemolytic on blood agar; does NOT form spores (unlike bacillus and clostridium); catalase positive

2) Virulence: Induces phagocytosis --> Listeriolysin O
lyses phagosome and escapes into cytosol --> use host actin cytoskeleton to create a tail and propel itself to adjacent cells --> spreads to bloodstream *similar to Shigella pathogenesis*

3) Clinical: Diarrhea with fever (listeria food poisoning); flu-like symptoms in pregnant women --> can lead to miscarriage or neonatal meningitis; also meningitis in elderly

4) Epi: livestock pathogen; resistant to cold temperatures; foodborne (contaminated refrigerated dairy products e.g. milk, soft cheese); disproportionately affects pregnant women

5) Treatment: ampicillin + gentamycin; prevention with proper food handling


Clostridium perfringens
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

C. perfringens - normal flora of large intestine, skin, vagina

1) ID: Large Gram-positive spore-forming bacillus; obligate anaerobe; immotile; double zone of beta hemolysis on blood agar

2) Virulence: Alpha toxin (phospholipase C) lyses RBCs, WBCs, platelets --> necrosis and gas gangrene; Enterotoxin alters cell membrane --> fluid loss; degradative enzymes e.g. DNAse, collagenase, proteases help infection spread

3) Clinical:
A. Myonecrosis (gas gangrene) - fermentation of muscle CHO yields H2 gas and rapidly spreading infection --> necrotizing enterocolitis or fasciitis
B. Food poisoning - late onset (from consuming spores, which germinate in gut and then produce toxin)

4) Epi: spores found in soil; infection associated with military combat or motorcycle accidents

5) Treatment: debridement, hyperbaric 02 treatment, IV penicillin G


Clostridium botulinum
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

C. botulinum - in soil and aquatic sediments

1) ID: Large Gram-positive rods; obligate anaerobe; immotile; detect toxin via mouse bioassay

2) Virulence factors: Botulinum exotoxin - neurotoxin cleaves SNARE proteins at motor neuron endplates --> blocks acetylcholine release --> descending paralysis

3) Clinical manifestations: NO fever or sepsis, affects PNS only bc cannot cross BBB; food poisoning with progressive descending flaccid paralysis and ptosis --> respiratory failure; "floppy baby" syndrome --> low mortality from infant botulism

4) Epidemiology: (adults) ingestion of preformed toxins in contaminated canned foods; (babies) colonization of intestine due to ingestion of endospores in honey; one of the most potent exotoxins known

5) Treatment/Prevention: Immediate horse antitoxin + supportive critical care; infection does NOT confer immunity (as with tetanus)


Clostridium tetani
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

C. tetani - common in soils
1) ID: Large Gram-positive, racquet-shaped bacillus ; obligate anaerobe; spore-forming

2) Virulence: Spores embed at wound site --> release tetanus toxin (tetanuspasmin) --> travels retrograde to CNS --> subunit B binds and A enters neurons and cleaves SNARE at synaptic vesicle membranes--> blocks inhibitory neurotransmitter release of GABA and Glycine at synapses of Renshaw cells --> prolonged muscle spasms

3) Clinical: spastic paralysis, starts with lock jaw --> arched back; high mortality rates from respiratory failure

4) Epidemiology: rare due to immunization, 02 sensitivity; common from puncture wounds (barbed wire, rusty nails)

5) Treatment/Prevention: passive (immunoglobulin) and active (tetanus toxoid) immunization; recovery from tetanus does not confer immunity (As with botulism)


Clostridium difficile
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

C. difficile - normal flora of large intestine, opportunistic pathogen

1) ID: Large Gram-positive spore-forming bacillus; motile, obligate anaerobe; v hard to culture --> non-hemolytic, rhizoid colonies on blood agar; catalase + indole + urease negative; ID via toxins in stool culture, enzyme immunoassay for toxins A and B, real time PCR

2) Virulence: Toxins-mediated i.e. no direct bacterial invastion; TcdA (bind brush border of enterocyte --> Watery diarrhea) and TcdB (actin depolymerization --> cell death and pseudomembrane formation)

3) Clinical: can cause spectrum of disease processes
A. Asymptomatic carrier
B. Disruption of normal flora by antibiotics --> colonization of intestine by C. difficile --> watery diarrhea with abdominal cramping and pseudomembrane covering
C. Mild pseudomembranous colitis

4) Epidemiology: one of the most common nosocomial infections; suspect in patient with diarrhea who received antibiotics (esp. clindamycin) in last 2 mos or when diarrhea occurs 72 hrs+ post hospitalization

5) Treatment: judicious use of antibiotics e.g. oral vancomycin, probiotic preparations, barrier precautions


What are the 6 A's - the risk factors for C. difficile-associated diarrhea (CDAD)?

1. Acquire spores via fecal-oral route *most important factor* --> germinates in large intestine
2. Antibiotic use (associated with cephalosporins, fluoroquinolones e.g. cipro, and clindamycin)- second hit that disrupts the normal colonic flora and messes with secondary bile salt numbers --> allows spores to infect
3. Advanced age
4. Admitted to hospital - most common place where spores are acquired
5. Acute illness
6. Acid suppression


1) Describe general features of Chlamydia incl how they multiply in host

2) Describe ID and clinical characteristics of the three species in the Chlamydia genus:
A. C. trachomatis
B. C. pneumoniae
C. C. psittaci

1) Chlamydia: Gram indeterminate (bc no muramic acid in peptidoglycan) --> visualize via Giemsa stain; diagnose via NAAT; obligate intracellular parasites that target epithelial cells of mucous membranes

Pathogenesis: elementary body phagocytosed and enters the cell --> differentiates into reticulate bodies--> replicate and reorganized into EBs in cytoplasm--> Cell ruptures and EBs released to restart cycle

2A) C trachomatis
ID: PCR test from vaginal swab or urine; ThinPrep cervical specimen for Chlamydia + cervical cancer
i. Serotypes A-C: ocular trachoma --> leading cause of preventable blindness
ii. Serotypes D-K: genital tract infections --> most common cause of bacterial STIs, majority asymptomatic but also watery discharge --> pelvic inflammatory disease
-neonatal pneumonia - staccato cough
-inclusion conjunctivitis --> all newborns given eythromycin eye drops; presents later than gonorrheal conjunctivitis
iii. Serotypes L1-L3: lymphogranuloma venereum (another STI) --> inguinal lymphadenopathy; complications lead to Reiter's syndrome (autoimmune response) - "can't see, can't pee, can't climb a tree"

2B) C. pneumoniae
ID: TWAR serotype, more common in elderly
Clinical: mild URT infections, atypical pneumonia (also seen in Legionella and Mycoplasma)

2C) C. psittaci
ID: transmitted from birds esp parrots
Clinical: hard to diagnose - fever, headache, sore throat

Treatment: macrolides + tetracyclines, assume coinfection with gonorrhea so give ceftriaxone


1) Describe general features of Rickettsia

2) Describe pathogenesis and clinical features of the following species in the Spotted Fever group of Rickettsia:
A. R. rickettsii
B. R. akari

1) Rickettsia: obligate intracellular parasite - cannot produce NAD+ or CoA; Gram negative coccobacilli but stains poorly (no cell wall); transmitted via arthropods vectors/reservoirs; treatment is doxycycline

2A) R. rickettsii - most virulent
i. Pathogenesis: transmitted via dermacenter ticks; bacteria attach to target endothelial cells via OmpA or OmpB --> induce phagocytosis --> escape and proliferate in cytosol--> actin tail-mediated motility and spread (like Shigella and Listeria) --> petechial rash
ii. Clinical: Rocky Mountain spotted fever --> rash at palms of hands and soles of feet, fever, headache, vasculitis

2B) R. akari
i. Pathogenesis: transmitted via mouse mite; targets macrophages, NOT endothelial cells as with most Rickettsia
ii. Clinical: Rickettsialpox --> dark eschar at site of the mite bite


1) Describe general features of Rickettsia

2) Describe pathogenesis and clinical features of the following species in the Typhus group of Rickettsia:
A. R. prowezekii
B. R. typhi
C. Orientia tsutsugamushi

1) Rickettsia: obligate intracellular parasite - cannot produce NAD+ or CoA; Gram negative coccobacilli but stains poorly (no cell wall); transmitted via arthropods vectors/reservoirs; treatment is doxycycline

2A) R. prowezekii
i. Pathogenesis: Humans are reservoir and vector is body lice; can cause epidemics esp in times of disasters; same mechanism as R. rickettsii but NO actin motility for cell to cell spread
ii. Clinical: Louse-borne epidemic typhus --> louse poops near bite and scratching introduces bacteria into body --> rash spreads from trunk to extremities, fever, headache and spares hands + feet + head (opposite of Rocky Mountain Spotted fever)
Can lead to arthralgia, myalgia, pneumonia, or encephalitis --> coma

2B) R. typhi
i. Pathogenesis: Rat is reservoir and vector is the rat flea, found in tropical seaboard regions
ii. Clinical: Murine endemic typhus --> milder than louse-borne typhus

2C) O. tsutsugamushi
i. Pathogenesis: reservoir is chigger
ii. Clinical: Scrup typhus --> disease occurs in Far east


For the following Gram indeterminate species, describe pathogenesis and clinical features:
1) Ehrlichia chafeensis
2) Anaplasma phagocytophilum
3) Coxiella burnetii

1) Ehrlichia chafeensis
A. Pathogenesis: reservoir is white tailed deer, vector is tick; multiply in morula = cytoplasmic vesicle; target phagocytes
B. Clinical: Human Monocytic Ehrlichiosis --> fever, anemia, and leukopenia

2) Anaplasma phagocytophilum
A. Pathogenesis: reservoir is white footed mouse, vector is tick; target is neutrophils
B. Clinical: Human Granulocytic Anaplasmosis --> fever and neutropenia, rare rash

3) Coxiella burnetii - v infectious, obligate intracellular
A. Pathogenesis: Reservoir is sheep and cattle, vector is tick; transmitted through aerosol inhalation
B. Clinical: NO rash; Self-limited illness with Q fever, headache, pneumonia, hepatitis


Mycoplasma pneumoniae:
1) ID
2) Virulence factors
3) Clinical manifestations
4) Epidemiology
5) Treatment/Prevention

M. pneumoniae
1) ID: Gram indeterminate (no cell wall); smallest organism that can be cultured (on Eaton's agar) --> colonies have dense mulberry shape; culture requires cholesterol bc its only bacteria that has cholesterol in cell membrane

2) Virulence: membrane glycolipids and proteins (Ab are self-reactive); attaches to ciliated respiratory epithelial cell via adhesin

3) Clinical: atypical pneumonia (like Legionella and Chlamydia) = walking pneumonia--> lower respiratory tract infection with gradual onset (due to long incubation) of fever + cough --> formation of IgM cold agglutinins --> clumping of RBC in cold temps

4) Epi: transmitted via respiratory secretions (aerosol inhalation); more commonly occurs in adults



1) Borrelia burgdorferi
B. Pathogenesis + Virulence factors
C. Clinical manifestations

2) Borrelia recurrentis
B. Pathogenesis
C. Clinical manifestations

1) B. burgdorferi
A. ID: Gram negative, motile bc of endoflagella, coiled cell wall, difficult to culture; can be visualized via Giemsa or Wright's stain; test via ELISA and Western Blot
B. Pathogenesis: in NE USA; vector is deer tick - Ixodes scapularis; reservoirs are white footed mouse (for tick larvae) and white tailed deer (for adult ticks); virulence factors are Osps (antigenic variation to evade immune system)
C. Clinical: Lyme disease --> all stages curable with antibiotics (doxycycline and IV ceftriaxone for later stages)
i. Early infection (7 to 10 days) - erythema migrans (bull's eye rash) + flu-like symptoms (fever, chills)
ii. Disseminated infection (days to months) - cardiac (heart block) and neurologic symptoms (bilateral Bell's Palsy)
iii. Persistent infection (months to years) - Lyme arthritis, encephalopathy

2) B. recurrentis
A. ID: Gram negative, motile, coiled cell wall
B. Pathogenesis: reservoir is small animal and vector is human body louse
C. Clinical: Endemic relapsing fever --> sudden onset/end with single relapse



3) Leptospira interrogans
B. Pathogenesis
C. Clinical manifestations

4) Treponema pallidum
B. Pathogenesis
C. Clinical manifestations

3) L. interrogans
A. ID: Gram negative, motile, coiled cell wall, difficult to culture; associated with water sports
B. Pathogenesis: reservoir is rodents and vector is dogs, livestock, wild mammals; infection usually indirect (e.g. via animal urine in water)
C. Clinical: (early infection) asymptomatic or red eyes without pus, mild fever; (systemic disease when bacteria travels through blood) Leptospirosis or Weil's disease - kidney dysfunction, renal dysfunction and jaundice

4) T. pallidum
A. ID: Gram negative, motile; reagin Ab are generated upon syphilis infection --> nontreponemal (VDRL) or treponemal tests (FTA-ABs)
B. Pathogenesis: transmitted through any physical contact; active lesions and can invade any organ
C. Clinical: Syphilis stages
i. Primary - painless genital lesion (chancre) can heal spontaneously
ii. Secondary - systemic, maculopapular rash on hands/soles of feet, disseminated with secondary lesions
iii. Latent - serologic tests + but no clinical signs
iv. Tertiary - affects any organ e.g. meningitis, aneurysm of ascending aorta, Gummatous lesions in skin + bone (soft growth with necrotic center), Argyll Robertson pupils (react to accommodation but NOT light)
v. Congenital - developmental abnormalities (Saddle shins, saber nose, deafness)
*treat with penicillin --> can have Jarisch-Herxheimer rxn (fever and chills) due to release of cytokines


1) How is the peptidoglycan layer formed?

2) What is the MOA of beta lactam antibiotics in inhibiting this process?

3) What resistance to bacteria have to beta lactam antibiotics?

4) What is the pharma response to these resistant bacteria? Give two examples of these drugs

1) Transglycosylase enzymes join NAM and NAG monomeric sugars to make polysaccharide chains;
Transpeptidase enzymes (aka PBPs) join sugar-linked peptide side chains by crosslinking terminal D-ala-D-ala with Gly --> strengthens cell wall

2) Beta lactam antibiotics are only bactericidal in growing cells (which are producing peptidoglycan); D-ala-D-ala analogs
MOA: bind covalently/irreversibly to transpeptidase/PBP --> enzymes non-functional --> fewer peptide crosslinks --> weak cell wall --> cell death due to osmotic lysis

3) Produce serine beta lactamases --> similar to transpeptidases so beta lactam antibiotics bind them instead --> bigger active site so water can come in -> hydrolyzes active site linkage and inactivates drug

4) Beta lactamase inhibitors: bind the beta lactamases covalently and inactive irreversibly; have NO antibacterial activity --> paired with Beta lactam antibiotic (and increase their half life)
A. Clavulanic acid
B. Avibactam - broader spectrum, does not contain beta lactam core


For each subset of beta lactam antibiotics, list examples + describe utility + adverse effects:

1) penicillins
A. Common
B. Anti-staph
C. Extended spectrum

2) cephalosporins
1st - 5th generations

3) monobactams

4) carbapenems

1) Penicillins: oral or IV, rapidly cleared, non-toxic at high amounts but side effects can include GI upset or allergic reactions (sub with 2nd Gen+ve cephalosporins)
A. Common - Penicillin G: acid labile, good for Gram + and -
B. Anti-Staph - Oxa, Naf, Methicillin: acid stable, good for Gram +ve but not Enterococci, anaerobic, or Gram -ve; intrinsically resistant to beta lactamases
C. Extended spectrum - Amoxicillin: acid stable, good activity against Gram -ve; used in combo with clavulanic acid (beta lactamase inhibitor) --> Augmentin e.g. for pasteurella

2) Cephalosporins: oral or IV; can have hypersensitivity (fever, skin rash. hemolytic anemia)
A. 1st Gen - cefazolin, Gram +ve, surgical prophylaxis
B. 2nd Gen - clofazamin, more Gram -ve e.g. for M. leprae (lepromatous leprosy)
C. 3rd Gen - ceftriaxone, most Gram -ve coverage
D. 4th Gen - cefepime, true broad spectrum drug, penetrates CNS
E. 5th Gen - Ceftolozane (combo as Zerbaxa) --> MDR Gram -ve; Ceftaroline --> MRSA

3) Monobactams: IV, active Against Gram -ve but not Gram +ve (does NOT bind transpeptidases)

4) Carbapenems: broad spectrum --> good for Gram +ve and -ve; penetrate CNS
A. Imipenem, half-life increased in combo with cilastatin


1) What is MRSA and what its mechanism of resistance?

2) Describe how vancomycin can be used to treat MRSA?

3) Describe vancomycin resistance

1) Most bacteria are resistant to penicillin; Methicillin was preferred bc it is inherently resistant to beta lactamases
MRSA = Methicillin resistant S. Aureus
MOA: acquired mecA gene --> altered PBPs with decreased affinity for beta lactam antibiotics (penicillins e.g. methicillin, cephalosporins except 5th gen, beta lactamase inhibitor combos, etc)

2) Vancomycin: active against Gram +ve; binds D-ala-D-ala -> prevents formation of polymers of NAG and NAM that form backbone of peptidoglycan --> cell lysis

3) Vancomycin resistance: D-ala-D-ala switch to D-ala-D-Lac (via vanHAX operon) + peptidoglycan layer thickens--> vancomycin cannot bind
-First resistance in Enterococci (VRE) --> transferred to S. aureaus (VISA) through horizontal gene transfer


Describe the MOA of the following drugs:

I. Disrupt bacterial membranes
A. Daptomycin
B. Polymyxin

II. Disrupt synthesis of peptidoglycan precursors
A. Bacitracin
B. Fosfomycin
C. D-cycloserine

I. Disrupt bacterial membranes
A. Daptomycin: forms pore in membranes --> K+ loss without cell rupture (no release of toxins); for Gram +ve SSTI that involve MRSA
B. Polymyxin: Bind outer membranes of Gram -ve bacteria --> create perforations and increase permeability --> entry of other drugs; topical or IV

II. Disrupt synthesis of peptidoglycan precursors
A. Bacitracin: Gram +ve; inhibits lipid carrier of peptidoglycan subunits; topical bc nephrotoxic
B. Fosfomycin: Gram +ve and -ve; inhibits first committed step in cell wall synthesis (NAG--> NAM)
C. D-cycloserine: competitive inhibits enzymes that form D-Ala-D-Ala


What are the treatment guidelines for:
1) latent TB infection (LTBI)
2) culture +ve without HIV
3) culture -ve without HIV
4) TB + HIV coinfection

Isoniazid 6 OR 9 mos *gold standard*
OR Isoniazid + Rifapentine 3 mos
OR Rifampin 4 mos

2) Culture positive TB
A. Initial phase: INH + RIF + PZA + EMB for 2 mos
B. Continuation phase: INH + RIF + PZA + EMB for 6 mos
OR INH + RIF + EMB for 9 mos (longer timeframe if you dont take PZA)

3) Culture negative TB
A. Initial phase: INH + RIF + EMB + PZA for 2 mos
B. Continuation phase: INH + RIF for 2 mos

4) TB + HIV coinfection (more aggressive)
-2x or 3x weekly multidrug therapy for 9-12 mos
-INH + PZA + EMB + Rifabutin (RIF has adverse rxn with antiretrovirals)


What is the rationale for the multiple drug approach to active TB treatment?

What is de facto monotherapy?

Multidrug therapy - mutants that emerge during treatment will be killed by the other drugs --> decrease number of resistant cells per lesion
*no cross resistance among major drugs used in TB treatment*

De facto monotherapy - bug is susceptible to only one drug of the multidrug therapy
-Due to preexisting resistance, poor distribution of drugs to tissues, differential targeting of bacterial forms (active vs dormant)


[TB treatment] For Isoniazid (INH), describe:
Active form
Adverse effects
Metabolism incl genetic implication
Resistance mechanisms

Isoniazid (INH):
-Activation: prodrug activated by bacterial KatG catalase-peroxidase --> INH-NAD
-Targets: bactericidal against extracellular AND intramacrophage mycobacteria
-Administration: oral (small hydrophilic molecule)
-MOA: inhibits Fab1 enzyme w/in NADH binding pocket of the FAS-II system --> can no longer synthesize the mycolic acid in the myobacteria cell wall
-Adverse effects: hepatitis and peripheral neuropathy (bc INH resembles B6 --> need to supplement with pyrodoxine B6)
-Metabolism: inhibited by acetylation by liver N-acetyltransferase; rapid acetylaters will have to be given more often
-Resistance: mutations of KatG, NADH binding pocket of Fab1, increased expression of Fab1


[TB treatment] For Rifampin (RIF), describe:
Active form
Adverse effects
Advantages of rifabutin and rifapentin over RIF

Rifampin (RIF)
-Activation: N/A, not a prodrug
-Targets: bactericidal against extracellular and intracellular mycobacteria, Gram -ve and +ve bacteria, and chlamydia
-Administration: oral
-MOA: Inhibits bacterial transcription elongation by binding to bacterial RNA polymerase
-Adverse effects: induces cyp p450 to increase elimination of other drugs, turns body fluids red/purple
-Resistance: mutations in gene encoding beta subunit of RNAP
-Rifabutin and Rifapentin are more potent, longer half lives, and less affected by cyps --> used with other medications e.g. HIV antiretroviral therapy


[TB treatment] For Pyrazinamide (PZA), describe:
Active form
Adverse effects

Pyrazinamide (PZA)
-Activation: converted to active Pyrazinoic acid form by PcnA bacterial enzyme
-Targets: bactericidal against dormant Mtb; need to use with drugs that kill active, growing cells to avoid de facto monotherapy
-Administration: oral
-MOA: Inhibits trans-translation process that rescues stalled ribosomes
-Adverse effects: hepatotoxicity
-Metabolism: --
-Resistance: PcnA mutations


[TB treatment] For Ethambutol (EMB), describe:
Active form
Adverse effects esp in children

Ethambutol (EMB)
-Activation: N/A, not a prodrug
-Targets: bacteriostatic, synergistic with other drugs e.g. INH
-Administration: oral, mostly excreted in urine
-MOA: inhibits fast growing extracellular Mtb by blocking extension of galactan protein
-Adverse effects: R/G color-blindness, dont give in children where its difficult to test vision
-Resistance: emerges easily, use in combo


What is the most important mortality rate to consider? What are the most common causes?

What is the most common exposure pathway? What are other common modes of transmission?

Infant mortality rate - mortality in 1st year per 1000 live births; leading cause of mortality is malnutrition-induced infant diarrhea (post-weaning), then pneumonia; most common infectious causes include rotavirus, Shigella/Salmonella, ETEC

Fecal-oral pathway (personal contact); other modes include food/water borne, blood borne, vector borne, or animal borne (zoonoses)


Give examples of the following causes of food-borne disease:
1) Foreign objects
2) Bacterial infections
3) Bacterial toxins
4) Viruses
5) Parasites
6) Toxic chemicals
7) Radioactivity
8) Vectors

1) Foreign objects e.g. straw, glass

2) Bacterial infections e.g. due to antibiotics that affect gut microbiome --> Listeriosis, Salmonellosis, Bovine TB, ETEC

3) Bacterial toxins e.g. Cholera toxin, Staph aureus, EHEC, Marine (scombroid, fugu)

4) Viruses (fecal-oral route) e.g. polovirus, norovirus, Hep A

5) Parasites e.g. Acute (Giardia, amoeba), Chronic (trichinosis)

6) Toxic chemicals in food e.g. pesticides, lead in water, mercury in fish

7) Radioactivity esp in Japan

8) Vectors - vector-borne diseases related to water e.g. malaria, dengue, river blindness


List bacteria that are facultative intracellular in macrophages or target macrophages.

List other facultative intracellular bacteria

Facultative intracellular in macrophages (can enter macrophages and cause disease spread):
-S. typhi (facultative intracellular in macrophages)
-M. tuberculosis (bacteria contained in caseating granulomas of necrotic macrophages, prevents phagolysosome fusion)
-Brucella (Facultative intracellular inside macrophages and prevents phagolysosome fusion)
-M. leprae (tuberculoid leprosy - infection contained within macrophages, lepromatous leprosy is not)
-B. anthracis (either obligate aerobe or facultative anaerobe inside macrophage)
-L. pneumophila (live in macrophage or amoeba)
-R. akari (bacteria targets macrophages and causes dark eschar)

Other facultative intracellular:
-Shigella (in M cells of Peyer's patches)
-Neisseria gonorrhea (in PMNs e.g neutrophils)
-Franciscella tularensis
-Listeria monocytogenes (using actin rocket inside the cell, tumbling motility via flagella outside)


List bacteria whose pathogenesis include actin polymerization and propulsion via actin tail

1) Shigella - S. dysenteriae
2) Listeria - L. monocytogenes
3) Rickettsia - R. ricketsii (through Omp proteins)


List two bacteria whose pathogenesis involves the ribosylation and inactivation of EF-2

1) Pseudomonas aeruginosa
2) Coynebacterium diphtheriae


List bacteria whose clinical manifestations include osteomyelitis

1) Staph aureus (most common cause)
2) Salmonella typhi (most common in sickle cell/asplenics)
3) Pseudomonas aeruginosa (common in diabetics/IV drug users)
4) Brucella - if infection from farm animals
5) Pasteurella - if infection from dog/cat bite spreads


List bacteria that cause atypical pneumonia

1) L. pneumophila (pneumonia w/ hyponatremia, diarrhea)
2) M. pneumoniae (walking pneumonia whose chest X ray looks way worse than clinical presentation, more common in young adults)
3) C. pneumoniae (walking pneumonia, more common in elderly)


List bacteria that result in the formation of a pseudomembrane

1) Corynebacterium diphtheriae - thick, grey pseudomembrane in upper respiratory tract (throat and nasopharynx) due to cell death (exotoxin ribosylates EF2)

2) Clostridium difficile - B exotoxin depolymerizes actin --> causes cell death --> yellow-ish pseudomembrane in colon (pseudomembranous colitis)