bacterial pathogenesis Flashcards

1
Q

definition of virulence factor

A

a component or trait of a pathogen that allows it to cause disease in a susceptible host

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2
Q

limitations of koch’s postulates

A

1) sometimes the organism is long gone by the time disease symptoms appear
2) many organisms are not cultivable
3) the disease may be specific to humans

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3
Q

T3S

A

“injectisome” functions as a hypodermic syringe; translocated effector proteins target various components and organelles of the host cell, corrupting their normal function for the benefit of the pathogen.

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4
Q

benefits of secreted virulence factors

A
  • subverting host cell pathways to permit growth of intracellular pathogens
  • preparing for the next round of infection: adhesins/invasins may be “premade” to be used later at a different site or in a different host
  • preventing cell death
  • remodeling the cell cytoskeleton so that the pathogen can attach better or move around the cell better
  • getting around host defenses
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5
Q

pathogenicity is

A

acquired in quantum leaps rather than through gradual evolution

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6
Q

example of virulence plasmid

A

Shigella

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7
Q

example of phage

A

Cholera toxin

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8
Q

example of pathogenicity island

A

LEE: encodes T3S system and intimin; intimin does not have a receptor, so LEE brought one along

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9
Q

Stanley Falkow

A

1988 - molecular koch’s postulate

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10
Q

Falkow’s postulates

A

the gene(s) encoding the phenotype should be associated with pathogenic strains

inactivation of the gene(s) results in a reduction in virulence

restoration of the gene(s) into the avirulent mutant reestablishes virulence

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11
Q

virulence factors-1

A

colonization factors
adherence factors
invasion factors

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12
Q

virulence factors-2

A

toxins

immune evasion factors

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13
Q

other virulence factors (3 kinds)

A

motility
iron acquisiton
biofilms

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14
Q

adherence factors

A

the successful pathogen must compete with normal flora, overcome electrostatic repulsion.

initial host-pathogen interaction requires the functions of a bacterial adherence factor of a host receptor

bacterial adherence is often mediated by adhesins

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15
Q

invasion factors

A

distinguish between cell and tissue invasion

cell invasins promote internalization of pathogen into a cell

some do both

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16
Q

internalin

A

listeria invasion and cell-to-cell spread is mediated by protein named internalin

perio pathogen p. gingivalis has internalin homolog

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17
Q

membrane ruffling

A

salmonella uses T3S to secrete effectors that induce membrane ruffling

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18
Q

bacterial toxins (two types)

A

1) lipopolysaccharides associated with the cell wall of gram-negative bacteria; the LPS component of the gram negative outer membrane is also named endotoxin because of its association with the cell wall
2) proteins released into the extracellular environment (most of the protein toxins are exotoxins since they are released from the bacteria that act on host cells at a distance

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19
Q

endotoxin

A

LPS is composed of lipid A and core polysaccharide and O antigen and is released upon lysis of the bacterium during infection

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20
Q

lipid A

A

carries the endotoxin activity

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21
Q

O side chain

A

antigenic portion of LPS

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22
Q

endotoxemia

A

endotoxin in the blood

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23
Q

circulatory system effects of endotoxin

A

leukopenia followed by leukocytosis

24
Q

other effects of endotoxin

A

effects on on metabolic and liver functions
decreased iron availability
hypoglycemia: abnormally low glucose levels
cellular death
organ necrosis
shock
death

25
2 broad classes of exotoxins
cellular targets | intracellular targets
26
cytolytic exotoxins
usually degradative enzymes or cytolysis - hemolysis, tissue necrosis, may be lethal when administered intravenously
27
intracellular targets
A-B dimeric exotoxins (B, binding; A, active) B associated with absorption to cell surface and transfer of A across membrane. Once internalized, A enzymatically disrupts cell function. receptor-mediated endocytosis (exotoxin internalization) ADP-ribosylation of intracellular target host molecule
28
3 major types of bacterial cytolysis based on mechanisms of action
hydrolyze membrane phospholipids (phospholipases) thiol(-SH)-activated cytolysins alter membrane permeability by binding to cholesterol detergent-like activity on cell membranes; rapid rate of lysis
29
how do AB toxins work?
1. bacterium produces and releases exotoxin 2. b (binding) component of exotoxin attaches to host cell receptor. 3. A-B exotoxin enters host cell by endocytosis. 4. A-B exotoxin enclosed in pinched-off portion of plasma membrane during pinocytosis. 5. A-B components of exotoxin separate. The A component alters cell function by inhibiting protein synthesis. The B component is released from the host cell.
30
examples of A-B exotoxins
anthrax toxin shig toxin cholera toxin tetanus toxin
31
anthrax toxin
three separate proteins - protective antigen (PA); edema factor (EF); lethal factor (LF)
32
shiga toxin
chrom.-encoded - among most potent of all biologic toxins; inhibition of protein synthesis
33
cholera toxin
results in hypovolemic shock and death if no fluid/electrolyte replacement therapy
34
tetanus toxin
among most potent of all toxins, released upon lysis; spastic paralysis with trismus and spasms
35
botulinum toxins
among the most potent of biological toxins; flaccid paralysis and death
36
2 types of host defenses
non-specific | immune-mediated
37
strategies to avoid phagocytosis
- hide inside cells - turn on flagellar motors - provoke minimal inflammatory response - secrete something to inhibit phagocyte chemotaxis or phagocyte uptake - coat bacteria surface with host component to be recognized as self - inhibit phagocytosis
38
examples of antiphagocytic substances
``` capsule k antigen m protein/fimbriae protein A slime layer o antigen ```
39
intracellular pathogens may also avoid phagocytic killing by
inhibitng phagolysosome fusion surviving inside the phagolysosome escaping from the phagosome secreting aggressins
40
agressins
``` streptolysin O leukocidin exotoxin A adenylate A adenylate cyclase anthrax toxin EF ```
41
2 major mechanisms by which pathogens escape the humoral response
antigen mimicry | antigenic variation
42
antigen mimicry
the pathogen is naturally coated with antigens closely related to host constituents or borrows host constituents to coat itself with such that the immune system cannot distinguish between self and the pathogen
43
antigenic variation
the pathogen changes its antigen coat periodically to evade the ongoing immune response
44
3 criteria define phase variation
any need a bacterium may have to respond to rapidly changing environment occurs by high frequency reversible genetic mechanism no relationship between the varying trait and the underlying mechanism
45
3 criteria for antigenic variation
immune evasion, avoidance of immune selection occurs by spontaneous mutation (antigenic drift) occurs by a phase variation mechanism (when high frequency is needed)
46
what does most phase variation phenomena involve?
surface structures exception: phase variation of DNA modificaiton
47
how was phase variation recognized historically?
by variation of colony morphology (e.g. opacity) or of easily measurable phenotypes (e.g. motility)
48
capsule
all-or-none on/off variation in some Gm+ and Gm-
49
pili (fimbriae)
phase variation mostly affects transcription at major promoter
50
flagella
phase variation may affect different components of the flagellum
51
surface proteins
Gm+ well wall or GM- OM proteins such as transporters, receptors, virulence factors or enzymes may phase vary
52
LPS and LOS
enzymes that modify side groups of O-antigen may phase vary
53
regulatory proteins
global or specific regulators
54
advantage of regulatory proteins
advantage is that only one gene needs to phase vary to affect the expression of many genes
55
genetic basis of phase variation
short sequence repeats and slipped-strand misrepairing homologous recombination site-specific recombination (inversion of a DNA element; insertion and excision of DNA elements)
56
homologous recombination
expressed allele and silent repertoire frequency is higher than most other RecA-dependent HR events Less homology required than in standard Rec-A dependent HR additional cis-element required
57
site-specific recombination
conservative site-specific recombination can be lead to inversion, insertion or excision of DNA segment