Bacteria, Toxins, & Virulence Flashcards

1
Q

Koch’s Postulates

A
  1. Specific microbe is present regularly in characteristic lesions of the disease
  2. This microbe can be isolated and grown in vitro
  3. Injection of the cultured microbe into animals reproduces the disease in animals
  4. The specific microbe can be re-isolated from lesions of the disease in animals
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2
Q

Pathogen

A

A microbe capable of causing host or damage; includes classical and opportunistic pathogens; damage can result from direct microbial action or host immune response

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3
Q

Pathogenicity

A

The capacity of a microbe to damage a host

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4
Q

Virulence

A

Relative capacity of a microbe to damage a host

Compared by ID50 (minimally infective dose in 50%), DD50 (disease producing dose in 50%), and LD50 (lethal dose in 50%)

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5
Q

Peptidoglycan

A

Forms a rigid mesh surrounding the cytoplasmic membrane of bacteria

Basic subunit consists of two alternating sugars (GlcNAc and MurNAc) and a 5 amino acid tail hanging off of MurNAc terminating in D-ala-D-ala

Transglycosylation joins the MurNAc and GlcNAc residues of adjacent subunits

Transpeptidation cleaves the terminal D-ala and joins the amino acid tails, allowing cross-linking

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6
Q

Lysozyme

A

Enzyme present in many body secretions; contributes to innate host defenses against bacteria by hydrolyzing peptidoglycan at the glycosidic bond between MurNAc and GlcNAc

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7
Q

Gram Negative

A

Has an outer membrane containing LPS, lipoproteins, and porins; LPS is located exclusively in the outer leaflet of the OM and phospholipids are located in the inner leaflet

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8
Q

Gram Positive

A

Contains a single cytoplasmic membrane; cell wall contains greater degree of peptidoglycan cross-linking; cell wall also contains Teichoic acids, which form a repeating polyglycerol-P or polyribitol-P backbone; lipoteichoic acids help anchor the cell wall to the membrane

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9
Q

Lipopolysaccharide (LPS)

A

Contains lipid A, the toxic component of endotixin, a core polysaccharide, and an oligosaccharide that functions as an antigen (O antigen)

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10
Q

Bacterial ribosomes

A

30S + 50S = 70S

DNA is located in the cytoplasm so transcription and translation are coupled; polyribosomes transcribe on one mRNA molecule simultaneously and mRNA may be “polycistronic,” coding for multiple proteins

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11
Q

Bacterial cytoplasmic membrane

A

AKA “inner membrane” in gram-negative bacteria; lipid bilayer made up of phospholipids and proteins but no sterols; exhibits selective permeability, essentially impermeable to all charged substances including protons; only hydrophobic molecules smaller than glycerol can diffuse

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12
Q

Phases of the Bacterial growth curve

A
  1. Lag phase - physiological adjustment to new medium
  2. Exponential (logarithmic) phase of growth - rate of increase in cell mass is proportional to the cell mass already present; a constant interval of time is required for doubling cell mass (generation time)
  3. Stationary phase - growth plateaus as essential nutrients are consumed and toxic metabolites accumulate
  4. The number of viable bacteria decreases as autolysis occurs
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13
Q

Heterotrophic Bacteria

A

Bacteria that require an organic carbon source, includes most bacterial pathogens

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14
Q

Autotrophic Bacteria

A

Bacteria that obtain their carbon exclusively from CO2

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15
Q

Fastidious Bacteria

A

Bacteria that are deficient in one or more biosynthetic pathways and require, in addition to sources of carbon and energy, a number of essential growth factors (AAs, purines/pyrimidines, and inorganic ions)

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16
Q

Obligate Intracellular Bacteria

A

Bacteria that can only live within eukaryotic cells

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17
Q

Strict Aerobe

A

Requires oxygen, cannot ferment

Ex: Mycobacterium tuberculosis

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18
Q

Strict Anaerobe

A

Killed by oxygen; fermentative metabolism

Ex: Clostridium

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19
Q

Indifferent (Aerotolerant anaerobe)

A

Ferments in presence or absence of O2

Ex: Strptococcus pyogenes

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20
Q

Facultative

A

Respires with O2, ferments in absence of O2

Ex: E. coli, Staph aureus

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21
Q

Microaerophilic

A

Grows best at low O2 but can also grow without O2

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22
Q

Fermentation

A

Organic compounds serve as both electron donors and electron acceptors; no net oxidation of substrates occurs; undertaken by:

Strict anaerobes
Facultative & indifferent bacteria - grown under anaerobic conditions
Indifferent organisms (aerotolerant anaerobes)
Ex: Glucose –> Ethanol

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23
Q

Bacterial respiration

A

Carbon compounds are oxidized by passage through the respiratory chain located in the cytoplasmic membrane; molecular oxygen (aerobic) or inorganic substrates (anaerobic) are final electron acceptor

Glucose –> CO2

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24
Q

Sporulation

A

A response to adverse nutritional conditions; spores are highly resistant, dehydrated, and have no metabolic activity; they can survive for long periods of time under adverse conditions and germinate when conditions improve to convert back to vegetative cells

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25
Q

Gram positive cocci

A

Streptococci (pneumoniae, pyogenes)
Staphylococci (aureus - MSSA, MRSA)
Enterococci (faecium)

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26
Q

Gram negative cocci

A

Neisseria (meningitidis, gonorrheae)

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27
Q

Atypical bacterial pathogens

A

Chlamydia, Mycoplasma

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28
Q

Gram positive rods - anaerobic

A

Clostridium (difficile, tetani, botulinum)

H. pylori

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29
Q

Gram negative rod - anaerobic

A

Bacteroides fragilis

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30
Q

Toxin Class - Spreading factors

A

Toxic enzymes secreted by microbial pathogens that break down the ECM, allowing the microbe to spread through tissues and cause disseminated infection

Ex: Collagenase, elastase, hyaluronidase

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31
Q

Toxin Class - Cytotoxins

A

Generally, toxins that act on the plasma membrane to cause cellular damage

Often toxins that insert into membranes and assemble into multimeric complexes that form pores, causing lysis of target cells

Ex: a-Hemolysin of Staph aureus

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32
Q

Toxin Class - Superantigens

A

Potent T-cell activators; bi-functional molecules that bind simultaneously to conserved region of MHC-II on antigen presenting cells AND to a conserved region of the TCR, generating a cytokine response that is independent of specific antigenic effects

Ex: Toxic Shock Syndrome Toxin (TSST-1) of Staph. aureus

Pyrogenic exotoxins of Strep. pyogenes

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33
Q

Cholera Toxin

A

Toxin Class: Intracellular signal disruption; produced by Vibrio Cholerae

B subunit binds the GM-1 receptor initiating endocytosis of the A subunit; in the cytosol, subunit A ADP-ribosylates the alpha subunit of the Gs protein, leading to its constitutive activation; Gs activates Adenylate Cyclase, which increases production of cAMP; cAMP binds the CFTR channel causing efflux of Cl- and water into the gut

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34
Q

Pertussis Toxin

A

Toxin Class: Intracellular signal disruption

ADP-ribosylates and inactivates the alpha subunit of inhibitory Gi protein; decreased inactivation of Gi leads to increased activity of Adenylate Cyclase and increased production of cAMP

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35
Q

Heat Stable Enterotoxin of E. coli

A

Toxin Class: Intracellular signal disruption

Activate guanylate cyclase on the surface of gut epithelial cells, leading to increased production of cGMP, causing secretory diarrhea

36
Q

Anthrax Toxin

A

Toxin class: Protein synthesis inhibitor, made by Bacillus anthracis

Edema Factor (EF) is an Adenylate Cyclase that enters target cells and produces cAMP (dependent on Ca2+ and Calmodulin within cells); leads to water efflux and edema

Lethal Factor (LF) is an endopeptidase that cleaves MAP kinase kinase, inactivating its function in signal transduction

37
Q

Diptheria Toxin

A

Toxin class: Protein synthesis inhibitor; made by C. diptheriae

Binds to a specific cell surface receptor via the B (binding) subunit; A (active) subunit is endocytosed and forms a pore in the endosome to enter the cytosol; A subunit inactivates elongation factor 2 (EF-2) by ADP-ribosylation, preventing protein synthesis by the ribosome and leading to cell death

38
Q

Shiga Toxin

A

Toxin Class: Protein synthesis inhibitor; made by Shigella dysenteriae and Enterohemorrhagic E. coli (EHEC)

RNA glycosidase that removes one adenine residue from the 28S RNA of the 60S ribosomal subunit

39
Q

C. diff Enteric Disease

A

Toxin Class: Protein synthesis inhibitor, produced by Clostridium difficile

C. diff toxin alters the actin cytoskeleton of target cells by transferring glucose to several Rho family GTPases, inactivating them

40
Q

Botulinum Toxin

A

Toxin Class: Neurotransmitter inhibition; produced by Clostridium botulinum

Inhibits release of ACh at neuromuscular junctions by cleavage of certain SNARE proteins; prevents muscle contraction, causing flaccid paralysis

41
Q

Tetanus Toxin

A

Toxin Class: Neurotransmitter inhibition; produced by Clostridium tetani

Inhibits the release of neurotransmitter from inhibitory interneurons by cleavage of certain SNARE proteins; causes sustained muscular contraction (tetany) of skeletal muscles

42
Q

Conjugation

A

Exchange of plasmid DNA between two physically linked bacteria, usually via conjugative plasmids (i.e. the “F” plasmid) that are self-transmissible; the F plasmid produces a special sex pilus that forms a direct connection with a recognized mating pair, allowing DNA replication of the plasmid across this cytoplasmic bridge

43
Q

Generalized transduction

A

Occasionally during the process of bacteriophage replication a piece of bacterial DNA is incorporated into the viral capsid; this viral particle is called a “transducing phage” and can inject this bacterial DNA into a new host cell, forming a stable recombinant

44
Q

Transformation

A

The ability of competent bacteria to take up naked DNA from the environment and incorporate it into their own genome

45
Q

Plasmid

A

Self-replicating, extra-chramosomal DNA element that is not essential for pathogen viability

May encode a variety of functions, including: r=Resistance to antibiotics
Virulence factors (toxins, adherence pili, capsule)
Metabolic functions (sugar utiization)
Self transmission
46
Q

Pathogenicity Island

A

Insertions of one or more genes when comparing the genomes of two strains of the same pathogenic species; often carry genes that encode virulence factors

Strains may transform from non-virulent to virulent via sequential acquisition of multiple pathogenicity islands

47
Q

Staphylococcus aureus

A

Gram + cocci carried asymptomatically by 30% of people in naris and perineum; produces alpha-hemolysin (alpha toxin) which forms a transmembrane pore in the membranes of infected cells, causing lysis; characteristic infections:

Cutaneous infection characterized by local abscess, often associated with the presence of a foreign body

Toxic Shock Syndrome

Pneumonia - hospital acquired

Bacteremia

Endocarditis

48
Q

Staphylococcus epidermis

A

Gram positive cocci, component of normal skin flora

Commonly found in localized skin infections, especially in the presence of foreign bodies; also common in infective bacterial endocarditis

49
Q

Streptococcus pyogenes

A

Gram + cocci

Causal pathogen of Group A Strep (pharyngeal infection) and post-strep disease (Rheumatic Heart Disease)

Skin and wound infections - diffuse cellulitis

50
Q

Streptococcus pneumonia

A

Gram + cocci, normal flora in upper respiratory tract

Common causal pathogen in many respiratory infections: pneumonia, sinusitis, bronchitis

Otitis media

51
Q

Streptococci viridians

A

Gram + cocci abundant in mouth; associated with dental caries

Oral viridians may gain access to blood strem following dental surgery, causing infective endocarditis

52
Q

Enterococcus faecalis

A

Gram + cocci, part of the normal intestinal flora

Frequent cause of nosocomial (hospital-acquired) infections of urinary tract, surgical wound, and biliary tract

Vancomysin-resistant enterococci (VRE) is an emerging problem

53
Q

Clostridium difficile

A

Anaerobic, gram + rod, part of the normal gut flora

Overgrowth of C. dif following antibiotic treatment in hospitals OR transmission by hospital staff leads to infective colitis, diagnosed by ELISA for toxin in stool

54
Q

Clostridium tetani

A

Anaerobic, gram + rod common in soil and GI tract of animals

Produces tetanus toxin which blocks inhibitory interneurons in the CNS resulting in tetanic paralysis of skeletal muscles

Infection may be prevented by vaccine (inactive toxoid) or treated by antitoxin (tetanus-immune IgG)

55
Q

Clostridium botulinum

A

Anaerobic, gram + rod found in soil & GI tract of animals; often grows in contaminated food under anaerobic conditions

Produces botulinum toxin which blocks ACh transmission at neuromuscular junctions, resulting in flaccid paralysis

56
Q

Escherichia coli

A

Gram negative rod, part of the normal gut flora; common infections include:

Traveler’s Diarrhea (via LT and ST of Enterotoxigenic E. coli [ETEC])

UTIs - caused by transplantation of E. coli from the GI tract

Abdominal infections - caused by release of colon contents into peritoneal cavity

57
Q

Pseudomonas aeruginosa

A

Gram negative rod, commonly found in the environment; often opportunistic, infecting immunocompromised patients; common infections include:

Chronic lung infections in patients with CF

Hospital-acquired infections - especially UTIs, pneumonias

58
Q

Neisseria gonorrhea

A

Gram negative cocci

Causative agent of gonorrhea; growth on mucosal surface incites an inflammatory response, resulting in purulent disgharge and local tissue invasion; prolonged infection may lead to scarring and fibrosis

Generally penicillin-resistant; often fluroquinolone resistant

59
Q

Bacteroides fragilis

A

Anaerobic, gram negative rod; makes up 1-2% of normal flora of the colon but associated with over 80% of intra-abdominal infections, generally abscesses

60
Q

Chlamydia trachomatis

A

Gram negative, obligate intracellular pathogen; common infections include:

Trachoma - chronic infection of conjunctiva leading to scarring and blindness

Genital infections - causative agent of non-gonococcal urethritis (in men)

Neonatal infections of infants born to mothers with genital infections, resulting in neonatal conjunctivitis and pneumonia

Treated with macrolides or tetracyclines

61
Q

Mycoplasma pneumoniae

A

Atypical bacteria lacking cell wall and containing sterols in the plasma membrane

Common cause of pneumonia in children and young adults; infection is generally mild and resolves over 1-4 weeks

Treated with macrolides or tetracyclines

62
Q

Spreading Factors

A

Toxic enzymes that facilitate the breakdown of ECM and the spreading of microbes throughout a tissue

Ex: hyaluronidase, elastase, collagenase

63
Q

alpha-Hemolysin

A

Staphylococcus aureus toxin; assembles into multimeric complexes that can form a pore in host cell membrane, causing lysis

64
Q

Superantigens

A

The most potent known T-cell activators; they act by binding to MHC-II molecules on antigen presenting cells and simultaneously to T cell receptors at a site that is different from the normal antigen binding site. This interaction stimulates excessive production of cytokines, causing pathological, systemic effects

65
Q

Diptheria Toxin - Mechanism

A

Diptheria toxin exists as an alpha-beta dimer; the beta (binding) unit facilitates endocytosis of the alpha (active) subunit; once intracellular, the alpha subunit inactivates elongation factor-2 (EF-2), preventing protein synthesis by the ribosome and leading to cell death

66
Q

Shiga Toxin

A

Produced by Shigella dysenteriae and enterohemorrhagic e. coli (EHEC)

Shiga toxin is an RNA glycosidase that removes one particular adenine residue from the large ribosomal subunit thereby inactivating it and preventing protein synthesis, which causes cell death

67
Q

Vibrio cholera

& heat labile E. coli enterotoxin

A

Binds go the ganglioside receptor on cell surfaces; once intracellular, the alpha subunit ADP ribosylates the alpha subunit of the stimulatory Gs G protein, which activates it; this leads to increased adenylate cyclase activity and higher concentrations of cAMP, which binds the CFTR channel causing active chloride secretion leading to secretory diarrhea

68
Q

Pertussis Toxin

A

ADP ribosylates the alpha subunit of the inhibitory Gi G protein, which inactivates it; this causes increased adenylate cyclase activity and increased cAMP levels

69
Q

Anthrax toxin

A

Edema factor (EF) - an adenylate cyclase; Ca2+ and Calmodulin dependent production of elevated cAMP within the target cell leading to water efflux and edema

Lethal factor (LF) - an endopeptidase that cleaves MAP kinase kinase protein, inactivating its function in cell signaling and leading to cell death

70
Q

Botulinum toxin

A

A toxic endopeptidase that inactivates specific SNARE proteins required for neuroexocytosis; causes flaccid paralysis of skeletal muscles by inhibiting release of ACh at neuromuscular junctions

71
Q

Tetanus toxin

A

A toxic endopeptidase that inactivates specific SNARE proteins required for neuroexocytosis; causes sustained muscular contraction of skeletal muscles by inhibiting the release of neurotransmitter from inhibitory interneurons

72
Q

Immunotoxins

A

Hybrid molecules which contain the active (A) fragment of a toxin chemically conjugated to a ligand for a specific receptor that differs from the receptor for the native toxin; often designed to kill tumor cells that display a tumor-specific receptor but not normal cells that lack that receptor

73
Q

Transposons

A

Discreet segments of DNA that are capable of moving themselves from one carrier of genetic information (genome or plasmid) to another; they are not capable of self-replication except as part of another self-replicating molecule

Conjugative transposons are capable of relocating from one cell to another

74
Q

Lysogenic conversion

A

The process by which a bacteriophage infects a host bacterial cell but, rather than enter the lytic cycle, the viral DNA (prophage) is integrated within the bacterial genome; this viral DNA often encodes for virulence factors that alter the phenotype of the newly infected lysogen

75
Q

Gram Negative Rods - Enteric

A

E. coli
Enterobacter
Klebsiella

76
Q

Gram Negative Rods - Non Enteric

A

Pseudomonas aeruginosa

77
Q

ETEC

A

Enterotoxigenic E. coli produces heat labile exotoxin, which activates Adenylate Cyclase to produce cAMP, leading to secretory diarrhea; it also produces heat stable exotoxin, which activates guanylyl cyclase in enteric epithelial cells, triggering fluid secretion

78
Q

Catalase

A

Reduces hydrogen peroxide to oxygen and water

Staph is catalase positive; strep and entero are gram negative

79
Q

Coagulase

A

Coagulase is an agent that inhibits spread of microbes by promoting the deposition of fibrin and helping to “wall off” and localize infection

Expression of coagluase by Staph aureus partially explains the formation of abscesses by staph infection

80
Q

Prevnar

A

Pediatric flu vaccine comprised of carbohydrate flu antigens conjugated with capsule proteins

81
Q

Which organisms produce glycocalyx?

A

Coagulase negative Staph

82
Q

Which organism produces an anti-phagocytic capsule?

A

Strep pneumo

83
Q

Which organism produces Dextrans?

A

Strep viridians; enhances adherence to damaged heart valves and teeth

84
Q

Which organism produces M protein?

A

Strep pyogenes

85
Q

Which organism produces antigenically distinct pili?

A

N. gonorrhea

86
Q

Mechanisms of resistance - E. faecium vs. E. faecalis

A

E. faecium - PBP5, VRE

E. fecalis - plasma encoded NSBL

87
Q

Narrow spectrum beta lactamases - Genes & Bugs

A

bla - Staph aureus (plasmid, all)
TEM1 - E. coli (plasmid, some)
SHV1 - Kleb. pneumo (chromosome, all)