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MCB C103 > Midterm 2 > Flashcards

Midterm 2 Flashcards

1
Q

Diphtheria toxin

A

Toxin catalyzes NAD ADP-ribosylating EF-2 (elongation factor 2)
Blocks prot syn
Diphthamide

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2
Q

Diphthamide

A

Susceptible aa is extensively post-translationally modified histidine
EF-2
Diphtheria toxin

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3
Q

Balifomycin

A

blocks vacuolar proton pump
prevents acidification of endosome
Prevent DT toxicity

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4
Q

Anthrax toxin EF

A

Edema factor
Competitively binds to P63
Cleaves MAPK kinases –> no TNF
Triggers pyroptosis

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5
Q

Anthrax toxin PA

A

Protective antigen
Necessary for activity of EF and LF
Binds to cellular receptor

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6
Q

Anthrax toxin LF

A

Lethal Factor
Competitively binds to P63
Cleaves MAPK kinases –> no TNF
Triggers pyroptosis

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7
Q

NALP1B (NLRP1)

A

Gene encoding inflammasome –> caspase-1 –> IL-1B
Activation of Nlrp1 –> pyroptosis
LF can be detected by NLRP1
LF sensitive mice (NlrP1+) are more resistant to spore
Protects against Bacillus anthracis infection
Human mphage are resistant to LT-induced pyroptosis –> v sensitive to spores

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8
Q

LPXTG motif

A
  • Gram + wall
  • Sequence that anchors surface proteins to peptidoglycan at the C-terminus
  • N-terminal signal sequence
  • Followed by hydrophobic seq and charged tail
  • Clipped by Sortase after secretion and covalently attached peptidoglycan
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9
Q

Quellung rxn

A

Treated w Ab –> swelling of capsule. Add India ink–> ink is excluded by capsule

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10
Q

Quorum sensing

A
  • @ low densities surface prot for adherence to host tissues are expr
  • @ higher densities, secrete virulence factors that kill host cells and facilitate spread of bac to new tissues and provide new food sources
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11
Q

M-protein

A
  • Surface exposed prot
  • Primary target of IgG
  • > 100 serologically distinct types
  • LPXTG (mem anchor)
  • Anti-phagocytic
  • Ab to some M-prot cross react with mammalian prot
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12
Q

Streptolysin O

A

SLO
Member of CDC family of hemolysins
Anti-SLO used to monitor infection by GAS
Can prevent chemotaxis of neutrophils
Can act as channel for intro of another secreted prot directly into host cells
Similarity to T3SS or B subunit

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13
Q

sil locus

A

Evolution of S. pyogenes –> skin infection
silAB: two component regulatory system
silCR: encodes 17 aa quorum sensing pep
silDE: encodes ABC transporters

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14
Q

Cholera toxin

A

AB5 toxin
Sec dependent
Secreted into and assembled in periplasm
Cell entry via retrograde translocation
Action: Catalyzes ADP-ribosylation rxn –> Transfers ADP-ribose from intracellular NAD to G-alpha –> ADP-ribosylated G-alpha is unable to hydrolyze GTP and thus remains active, stimulating adenylate cyclase resulting in incr of cAMP –> Causes large efflux of Na+ and H2O into gut lumen
Effects on immunity: Powerful immunogen –> anti-toxin Ab, Strong mucosal adjuvant, Blocks inflammation, Blocks inflammatory effects of TLR-activation in DC, Promotes DC IL-10 production (neg reg of innate immunity but promotes Ab production), Unintended consequence of stimulating acquired immunity to CT

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15
Q

Cholera Toxin Co-regulated Pilus

A

Class IV pilus
Mediates attachment
TcpC encodes lipoprotein that confers serum resistance
TcpG is disulfide isomerase that catalyzes interchain disulfide bond in TcpA
ToxT, essential tx factor of TCP expression
ToxT and ToxR activate fusion

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16
Q

Pertussis toxin

A

AB5 toxin
Action: ADP-ribosylation of a cysteine in the alpha subunit of an inhibitory trimeric G-protein (Gi) –> prevents the Gi complex from interacting with receptors, and so the complex remains bound to GDP and is unable to inhibit adenylyl cyclase –> PT has the same effect as CT although CT activates and PT prevents inhibition

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17
Q

Filamentous Haemaglutinin

A 
FHA
In Pertussis
 Surface prot
Ab target
Forms filamentous structures on bac surface that mediate adherence
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18
Q

Pertactin

A

In pertussis
Surface prot
Ab target

19
Q

Tracheal cytotoxin

A

TCT
in pertussis
Produces respiratory epithelial cytopathology seen during disease
Stimulates NOD1
Induces IL-1 in resp epi cells –> induces NO –> toxicity
Blocks chemotaxis and neutrophils in neutrophils

20
Q

Adenylate cyclase

A

Pertussis
Produces cAMP only in presence of calmodulin
Single chain “AB toxin”
Adenylate cyclase mutants are 3-4 logs less virulent (intranasal neonate mice) –> similar to PT-/- mut
Renders phagocytes non-phagocytic and unable to kill

21
Q

T3SS

A

Present both in pertussis and bronchiseptica

Induces apoptosis in macrophages

22
Q

BvgS

A

Master regulator for coordinate gene reg
periplasmic sensor histidine kinase
Phosphorylates BvgA –> incr affinity for BvgA activated promoters

23
Q

BvgA

A

Master regulator for coordinate gene regulation

transcriptional activator

24
Q

Vrg

A

Bvg-repressed genes

25
Q

Vag

A

Bvg-activated gene

26
Q

Type IV pili

A

Bac aggregation, Adhesion to host cells, Twitching motility, Pilus retraction, DNA transformation, In other bac sp, gliding motility, In V. cholerae, TCP is CT phage receptor

27
Q

pilE

A

pilin
Major pilus subunit, 20kDa
Pilin is syn as precursor w signal seq processed by PilD
Can switch b/w pilE1 and pilE2, incr variation

28
Q

pilD

A

Prepilin peptidase

29
Q

pilC

A

acts to counteract PilT mediated pilus retraction

30
Q

pilT

A

pilus retraction

31
Q

Gene regulation

A

Antigenic variation
A specific gene can be expressed or repressed as a response to enviro stim
BVG-regulated genes in Bordetella or ToxR-regulated genes in V. cholerae
Temporal change in gene expression but no genome alteration

32
Q

Genetic variation

A

Antigenic variation
For a subset of cells in a clonal pop, the genome is changes and gives rise to altered property
Ex. Pilus structure and antigenicity
May or may not be regulated, therefore may occur before bac are ever exposed to opsonic Ab that bind to pili

33
Q

pilS

A

silent gene

incr pilus variability

34
Q

Opacity

A

Outer mem prot
Mediate bac-bac aggregation and close interations w cells
12 diff Opa proteins encoded on the chromosome
Infec in human w Opa- bac results in emergence of Opa+ bac
Turned on or off in individual cells at freq = 10-4
CTCTT (leader peptide) Codon following is CCG (Ser) has to be in frame to allow syn of leader pep to allow sec mediated export

35
Q

Cytochalasin D

A

Blocks actin polymerization

36
Q

Inv

A

Outer mem prot
Sufficient to confer invasive phenotype on E.coli K12
Expr @ low T
Incr expr at low pH consistent w role during initial stages of infection

37
Q

Invasin

A

Bac surface prot

Binding to fibronectin receptor w high affinity triggers zipper mediated internalization

38
Q

Gentamicin

A

Prevents Yop expr

Stops prot syn by binding to ribosome

39
Q

Yops

A 
Syn relate to [Ca2+] and T
Secreted into cells
Inhibits phagocytosis in macrophages
Inhibits internalization in HeLa cells
Inhibits respiratory burst in neutrophils and macrophages
Inhibits cytokine expr (YopJ)
Block pyroptosis (YopM)
Promotes cell rounding and dissolution of focal adhesions and stress fibers (Yop H)
40
Q

YopJ

A

Inhibits cytokine expr
Plasmid-encode type II translocated effector
Appears to block immune signalling by adding acetyl group to kinases in MAP kinase or NF-kB pathways (inactivates)

41
Q

YopM

A

Type III translocated effector
Blocks pyroptosis
Stim PRK-phosphorylation of Pyrin (inactivates)

42
Q

YopH

A

Promotes cell rounding and dissolution of focal adhesions and stress fibers

43
Q

YopE

A

Type II translocated effector
Block phagocytosis
RhoGAP that inactivates Rho GTPases
Responsible for pyrin activation

44
Q

YopT

A

Type II translocated effector
Blocks phagocytosis
Protease that cleaves and inactivates Rho GTPases
Resp for pyrin activation

MCB C103 (3 decks)

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