Microbial Pathogenesis

Question 1

What is coagulase? Name a bacteria that is coag positive.

Answer 1

Accelerates clot-formation, and may be antiphagocytic. Employed by Staph aureus.

Question 1

Why are foreign bodies (artificial valves, etc.) prone to infection?

Answer 1

Because bacteria can adhere to these surfaces, but phagocytes adhere poorly (due to lack of selectins on these surfaces)

Question 1

What are the 3 types of gene regulation in bacteria?

Answer 1

1. Constitutive: always expressed, no regulation
   a. Rare, to conserve energy; most wild-type genes are regulated
2. Positive regulation: activator protein promotes RNA polymerase to bind promoters, facilitating expression
3. Negative regulation: repressor protein binds operator sequence, preventing transcription until removed
   a. More common than + reg. b/c loss of repressor allows continued gene expression, but loss of activator = loss of expressor and function
   b. Inducers: interact/bind w/activator OR repressor proteins (in + and - reg.)

Question 2

What are A-B toxins?

Answer 2

• A, active subunit, edocytosed
• B (often multiple) is binding subunit on cell surface
• Often ADP-ribosylation of G proteins
• Others alter ribosomes, inhibiting protein synthesis

Question 4

In what bacterium are carbapenemases most common?

Answer 4

• Klebsiella pneumoniae (KPC): multi-drug resistant bac hard to purge from hospitals
• Resistance spreading to G- and enterobacteriaceae

Question 5

Name an example of a pore-forming toxin.

Answer 5

Hemolysins (i.e., from lab)

Question 5

Describe bacterial fermentation.

Answer 5

• Used by obligate anaerobes to make energy
• Pyruvate -> various organic acids (may be diagnostic), CO2, or H
• Electrons transferred directly to organic acceptors (ineffective and slow)

Question 6

What are surfactants?

Answer 6

• Contain hydrophobic/philic groups and perturb bacterial cell membranes, leading to cell death
• Quaternary ammonium compounds (quats): cationic detergents not commonly used today b/c little activity against viruses, none against spores, and inactive in anion detergent

Question 7

Provide two examples of infections that do not lead to lifelong immunity. Why do re-infections occur in these cases?

Answer 7

• Chlamydia: poor immune response and efficient treatment
• Common cold: many serotypes, and antigenic variation

Question 7

What are the 2 key features of septic shock?

Answer 7

1. Blood culture are usually positive; in toxic shock, they’re negative because toxins in blood, not bac
2. Can cause pt. death even if bac killed b/c mediated by cytokines, i.e., TNF and IL-1, which act in absence of bac

Question 9

Cholera toxin has two fundamental subunits and causes the ADP-ribosylation of a G protein; the end result is secretion of fluids and electrolytes from cells. Cholera toxin is an example of:

Answer 9

An A-B toxin

Question 9

What are superantigens? Provide an example of a bacteria that uses these.

Answer 9

• Bind directly to class II MHC on APCs
• Results in large number of T cells releasing cytokines
• Example: Staph aureus and GAS toxic shock syndrome

Question 11

What are the 4 primary determinants of infection?

Answer 11

1. Number of microorganisms (exposure)
2. Virulence of microbe
3. Immune status of host (innate)
4. Past immune history of host (adaptive)

Question 11

What are the 7 stages of bacterial pathogenesis?

Answer 11

1. Transmission (exogenous or endogenous)
2. Evasion of physical defenses
3. Adherence
4. Colonization (and spread) - these first 4 form the incubation period
5. Symptoms produced by toxin production or invasion and inflammation
6. Host response (non-specific or specific)
7. Progression or resolution (persistent infection or clearance)

Question 12

What is the cause of most of the symptoms associated with most viral infections?

Answer 12

The hose immune response

Question 13

Why do certain bacteria stain Gram(+)?

Answer 13

• Extensive cell wall of G+ bacteria retains crystal violet dye

Question 14

Describe the regulation of the lac operon in E. Coli.

Answer 14

• LacI gene (constitutively expressed): upstream of operon, encodes repressor
• In presence of lactose, sugar transported into cell and converted to allolactose, inducer of lac expression
• Repressor releases from operator at low frequency, and binds allolactose in its presence, altering conformation (allostery), preventing repressor from binding to lac operator
• May lead to 1,000 fold increase of expression of lac genes and catabolism of all available lactose -> when lactose all used up, allolactose no longer formed, repressor molecules no longer allosterically altered and return to operator for repression

Question 16

Describe how IC pathogens (both obligate and facultative) get into cells, and subsequently, survive there.

Answer 16

• Receptor-mediated endocytosis
  1. Escape from phagosome
  2. Replication w/in phagosome (via inhibition of phago-lysosome fusion; blockage of acidification)
• Type III or IV secretion systems
• Transcytosis: allows access to subepithelial layers

Question 17

What is endotoxin?

Answer 17

• Leads to SIRS: fever, hypotension, tachycardia, tachypnea, and leukocytosis (released by Gram -)
  1. Damage to vascular endothelium
  2. TNF is central mediator
  3. LPS (lipid A) binds to LPS binding protein in serum (binds CD14 on macro surface; interacts with TLR, activating signaling cascade and various cytokines) - TNF beneficial in small amounts, but not in this case

Question 18

What are the 2 purposes of operons?

Answer 18

1. Help ward off LOF because decreased likelihood of evolutionary divergence
2. Single promoter/operon = co-regulation of genes, facilitating coordinate expression of functionally-related genes

Question 19

Name three bacteria that use IgA protease.

Answer 19

Strep pneumoniae, H. influenzae, N. gonorrheae

Question 20

What is the role of collagenase and hyaluronidase as virulence factors?

Answer 20

They allow spread through subcutaneous tissue

Question 21

What are the effects of endotoxin (LPS)?

Answer 21

• SIRS
• Fever: IL-1 and IL-6 from macros to hypothalamus
• Hypotension (shock): tumor necrosis factor- TNF (increased capillary permeability), NO (vasodilation), and bradykinin (vasodilation and increased capillary permeability)
• Inflammation: C5a via alternative pathway attracts neutrophils
• Coagulation (DIC): activation of tissue factor

Question 22

What is a metalloprotease? Name two.

Answer 22

Any protease enzyme whose catalytic mechanism involves a metal.

Examples: Botulism and tetanus toxins cleave snares, blocking neurotransmitter delivery.

Question 23

What is Protein A? Name a bacteria that uses it.

Answer 23

Binds to IgG, preventing activation of complement. Used by Staph aureus.

Question 24

What are alkylating agents?

Answer 24

• Gluteraldehyde: used to disinfect equipment
  1. Polymerizes/binds proteins in outer mem of G- bac and AA’s in cell wall of G+, alkylating (killing) proteins
• Ethylene oxide gas: used to treat heat-labile equipment
  1. Explosive, mutagenic, hazardous to skin -> thoroughly kills (sterilizes) all contaminants

Question 25

What oxidative respiration enzymes do strict aerobes have? Facultative anaerobes? Strict anaerobes?

Answer 25

• Aerobes: superoxide dismutase, catalase, and myeloperoxidase
• Facultative: may lack catalase
• Anaerobe: no superoxide dismutase, so killed in presence of O2 if more than brief exposure due to buildup of superoxide anions

Question 27

Define virulence.

Answer 27

A measure of a microbe’s ability to cause disease

Question 28

What are the 7 primary routes of infection? Why do these matter.

Answer 28

1. Respiratory (harder to control spread)
2. GI (Fecal-oral; can be limited by good sanitation)
3. Blood-borne
4. Sexual
5. Maternal-fetal or neonatal
6. Vector- or animal-borne
7. Fomites (Staph), soil (spores), water (i.e., Legionella)

These may not be important for predicting where the symptoms will occur, but they may come up in the PATIENT HISTORY, aiding in diagnosis.

Question 29

Approximately 5-20% of the population will harbor Group A Strep (GAS, the cause of strep throat) without illness. Accordingly, GAS should be considered:

Answer 29

Something between an opportunistic and frank pathogen. Most pathogens fall into this intermediary space.

Question 31

Describe the role of a capsule, and name 3 bacteria that use this virulence factor.

Answer 31

• Antiphagocytic (but, vaccine-derived antibodies can lead to opsonization)
• Strep pneumoniae, H. influenzae, N. meningitidis

Question 32

Describe the structure and importance of peptidoglycans in bacteria.

Answer 32

• Prominent target for antimicrobial therapy b/c unique to bac and disruption leads to cell lysis
• Backbone of repeating disaccharide (NAM and NAG) linked to form long chains by transglycosylase
• Pentapeptide (penicillin-binding protein) of AA’s attached to e/o and cross-linked by transpeptidases and carboxypeptidases
  a. Simple bond G-; pentaglycine interpeptide in G+
  b. Terminal D-ala pair (1 removed by carboxypep.)

Question 33

The time between initial exposure to a microorganism and the first appearance of symptoms is the:

Answer 33

Incubation period

Question 34

What is a curli?

Answer 34

Mediate binding of bacteria to endothelium and some EC proteins, like fibronectin. May beinvolved in disseminated intravascular coagulation seen in sepsis (binding factor XII).

Question 35

Name 5 bacteria that have polysaccharide capsules.

Answer 35

• Strep pneumoniae (G+); used in vaccine
• Neisseria meningitides (G-); used in vaccine
• Klebsiella pneumoniae (G-)
• Haemophilus influenzae (G-); used in vaccine
• Salmonella typhi (G-)

Question 36

List the Strep pyogenes virulence factors.

Answer 36

• Exotoxin-mediated: TSST (toxic shock superantigen), erythrogenic toxin (Scarlet fever superantigen)
• Pyogenic: hyaluronidase (cellulitis, necrotizing fasciitis, pharygitis)
• Non-suppurative: M proteins on pillus (Rheumatic fever and acute glomerulonephritis)

Question 37

Name four organisms that increase intracellular cAMP.

Answer 37

• Vibrio cholerae (via ADP-ribosylase -> cholera toxin)
• E. coli (via ADP-ribosylase -> labile toxin)
• Bordetella pertussis (via ADP-ribosylase)
• Bacillus anthracis (edema factor -> an adenylate cyclase)

Question 38

Name the virulence factors of S. aureus.

Answer 38

• Exotoxin-mediated:
  1. TSST (toxic shock, superantigen)
  2. Enterotoxin (gastroenteritis; food poisoning)
  3. Exfoliatin (scalded skin syndrome, protease)
• Pyogenic: skin abscess, osteomyelitis, endocarditis (enzymes causing inflammation and necrosis)
  1. Coagulase, hyaluronidase, leukocidin, lipase, and nuclease

Question 39

What is M protein? Name one bacterium that uses this virulence factor.

Answer 39

• Anti-phagocytic; bind Factor H, preventing C3b opsonization
• Strep pyogenes (G+, beta-hemolytic)

Question 40

List prominent normal flora in skin, nose, mouth, lungs, vagina/urethra, and large bowel.

Answer 40

• Skin: staph, strep, and pseudomonas
• Nose: staph
• Mouth: strep (and throat), bacteroides (gums)
• Lungs: pneumocystis
• Vag/urethra: staph, strep, G- rods
• Large bowel: strep, enterococci, G- rods, anaerobes

Question 41

What is mecA? What about vanA?

Answer 41

A gene acquired on transposon, inserted into chromosome, and encodes altered PBP resistant to binding by all beta-lactams (MRSA)

A gene acquired by some bacteria that is Vancomycin resistant by increasing thickness of cell wall (problematic b/c Vanc often the drug of choice for MRSA)