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ZZPathology undergraduate year 3, first term. > Bacteriology - cellular invasion > Flashcards

Bacteriology - cellular invasion Flashcards

1
Q

Chlamydia binding

A

Probably many receptors. cell-surface exposed PDI may be bound by EB and have an enzymatic role in entry.

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2
Q

Chlamydial entry - actin rearrangements.

A

Requires Rac1 dep remodelling.

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3
Q

Chlamydial Rac1 remodelling

A

Injection of Tarp, phosphorylation –> recruitment of Sos and Vav (Rac1 GEFs) and Abi-1 –> WAVE complex activity –> Arp2/3.
Possible role for Ct694.

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4
Q

Chlamydial transition EB –> RB

A

EB outer proteins are cross-linked. Disulphide bonds are reduced on internalisation –> nucleoid decondensation –> transcription.

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5
Q

Chlamydial effector secretion system.

A

T3SS

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6
Q

Chlamydial effectors inserting into inclusion membrane are called…

A

Inc

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7
Q

Inc-recruited proteins

A

Rab1, 4, 11; recycling endosome and Golgi related Rab GTPases.
Dynein for transport to perinuclear regions.

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8
Q

Chlamydial inclusion body formation and nutrient delivery.

A

Needs lipids (sphingolipids, cholesterol) for development.
a) Golgi fragmentation
b) Multivesicular bodies
c?) Non-classical routes e.g. lipid droplets

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9
Q

Inhibition of host cell death: Chlamydia.

A

Early block, late induction

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10
Q

Chlamydia: early block of apoptosis.

A

Stabilises inhibitor of apoptosis proteins.
Sequesters pro-apoptotic BAD.
Degrades BH3 only proteins. –> less Bax activation –> less cyt c release.

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11
Q

Intracellular bacteria - host cell death.

A

Inhibition - early chlamydia

Induction - late chlamydia, salmonella, shigella

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12
Q

Chlamydia - general

A

obligate intracellular pathogen.

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13
Q

Intracellular bacteria rapidly escaping cell cytoplasm.

A

Shigella, Listeria

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14
Q

Intracellular bacteria remaining withing the membrane bound vesicle.

A

Salmonella, Legionella pneumophila, Brucella abortus or Chlamydia spp

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15
Q

Chlamydial target cells

A

Epithelial cells.

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16
Q

Chlamydial entry sites

A

Occur at lipid microdomains.

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17
Q

Bacteria using raft-dependent entry pathways.

A

Shigella flexneri, Fim H-expressing E. coli, Brucella spp. and Chlamydia spp.
May confer special properties to the early inclusion/vesicle.

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18
Q

Chlamydial entry overview.

A

Adhesins, lipid microdomains, actin cytoskeleton reorganisation.

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19
Q

Intracellular bacteria uptake

A

Zipper, trigger, other mechanisms, phagocytosis.

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20
Q

Intracellular survival

A

Bacterial developmental transition.
Stay in the vacuole?
Manipulating the host cell

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21
Q

Manipulating the host cell

A

Bacteria containing compartment interacting with other compartments.
Altering host cell death
Inhibiting immune response.

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22
Q

Exiting the host cell

A

Host cell death.
Exocytosis.
Intracellular spread.

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23
Q

Host endocytotic pathway

A

Endocytosis/macropinocytosis –> EE –> late endosomes and acidification –> lysosomes.

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24
Q

Zipper mechanism

A

Express surface proteins.

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25
Q

Trigger mechanism

A

Inject effector proteins.

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26
Q

Result of chlamydial transition to RB.

A

New effectors by T3SS system.

Some insert into membrane - Incs.

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27
Q

Chlamydia inhibiting immune response

A

Block nuclear translocation of NFkB.

Increase NFkB degradation.

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28
Q

Inhibiting the immune response - mechanisms

A

Alter TLR binding
Alter NFkB
Alter cytokine mRNAs
Avoid autophagy.

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29
Q

Chlamydial cell escape

A

Transition from RB to EB and exit by host cell death.

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30
Q

Endocytic pathway. Endocytosis–>early endosomes.

A

Decrease inclusion of normal endocytic ones.

Use bacterial proteins to recruit Rabs (Chlamydia).

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31
Q

Endocytic pathway. EE –> LE.

A

GTPase Rab5 does this. Recruits EEA1

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32
Q

Endocytic pathway. LE –> lysosomes, mechanism

A

Calcium fluxes.

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33
Q

Endocytic pathway. LE –> lysosomes, mechanism; calcium fluxes.

A

Important in signalling maturation of lysosome. Ca++ influences calmodulin recruits Rab5 recruits PI3P

  • ->EEA1
  • -> v-ATPases
  • -> hydrolases.
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34
Q

Inhibiting Ca++ induced lysosomal fusion.

A

Unknown mechanism by cord factor. (TB).

Inhibited by phosphatidylinositol derivatives e.g. LAM.

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35
Q

LAM full name.

A

lipoarabinomannan

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36
Q

LAM action

A

Inhibits Ca++ mediated fusion; reduces development to a late endosome or acidification even if just on beads. With mannose caps inhibits recruitment of EEA1 as well.

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37
Q

Lysosomal conditions

A

Acidification via v-ATPase.
Acid hydrolases
Phagolysosomal oxidative burst.

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38
Q

Ways to survive acidification of lysosome.

A

TB: stop this.

Survive and divert hydrolases: Coxiella.

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39
Q

Coxiella survival of lysosome

A

Coxiella (passively continues down endosomal pathway until this point). Even just 5 minutes after internalisation it acidifies. Delayed acquisition of lysosomal enzymes such as cathepsin D.

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40
Q

How many acid hydrolases are there?

A

About 60.

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41
Q

Which bacteria decrease presence of acid hydrolases?

A

TB (none)

Salmonelal (very few, and few of their receptor, mannose-6-phosphate).

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42
Q

Mechanism of oxidative cell burst.

A

NADPH oxidase complex recruited by Rac (a Rho GTPase). Electron transfer occurs from NADPH to FAD to oxygen to make superoxide anions of various sorts.

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43
Q

Inhibiting oxidative cell burst

A

Superoxide dismutase by many pathogens.

Interfere with assembly/recruitment of NADPH oxidase.

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44
Q

Interfering with NADPH oxidase.

A

A phagocytophilum
Listeria
Salmonella

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45
Q

General intracellular replication points

A 
Use conditions to stimulate replication. 
Accumulation of nutrients. 
Space limitations
Alteration of vacuolar structure. 
Salmonella-induced filaments.
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46
Q

Space limitations in vacuole.

A

Acquisition of more lipids expands envelope of organelle.

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47
Q

Chlamydia Golgi fragmentation

A

Necessary for nutrient delivery.
Cleavage of Golgin-84 by CPAF gives access to sphingolipids by Golgi fragmentation. Formation of mini-stacks around the inclusion, triggers re-differentiation into EBs.

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48
Q

Interacting with other compartments - necessary for replication: delivery of nutrients.

A

Chlamydial Golgi-fragmentation.

Host proteins to facilitate accumulation.

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49
Q

Altering vacuolar structure for replication.

A

• Recruitment of mitochondria and ribosomes causes formation of ER like structure in which bacteria replicate (Legionella). Effector proteins via Dot/Icm.

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50
Q

Recruiting autophagy pathway for replication?

A

Coxiella. Autophagy vesicles loaded with membranes.

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51
Q

Role of salmonella induced filaments?

A

Formation of filaments probably causes intracellular survival and replication of bacteria but not fully understood.
Possible role for egress.

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52
Q

Bacteria using the zipper mechanism.

A

Listeria, Yersinia.

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53
Q

Listeria - general bacterial invasion mechanisms

A

Actin rearrangements.
Microtubule dependent.
Intermediate filaments and septins contribute to invasion efficiency.

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54
Q

Bacteria using intermediate filaments and septins

A

E. Coli, Salmonella, Listeria, Shigella.

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55
Q

Listeria binding proteins

A

Internalins InlA and InlB anchored to membrane via LPXTG or GW motifs. Leucine rich repeats critical for function. Determine cell tropism and host range.

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56
Q

InlA - binding.

A

Binds E-Cadherin, species specific. Has leucine rich curve which grips around it.
Listeria.

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57
Q

E-Cadherin clustering (bound by InlA)

A

Zipper, Listeria.

Binds catenins on cytoplasmic side. Interact with actin. Arp2/3 activated.

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58
Q

InlB - binding

A

Binds MET via LRR repeats which curve and grip. Listeria.

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59
Q

MET clustering due to InlB binding.

A

Mimics hepatocyte growth factor, but downstream recruits ABI and WAVE, and dynamin and cortactin.

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60
Q

Escaping the vacuole: Listeria.

A

Uses LLO and PLCs

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61
Q

LLO

A

Secreted by Sec. Thiol activated, reduced by GILT, optimally active at pH 5.5 Cholesterol dependent pore-forming toxin.

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62
Q

Action of LLO

A

Forms pore, interferes with iron gradients so no maturation and fusion of endosome. PLCs actually degrade vacuole.

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63
Q

Intracellular motility: Listeria

A

Surface protein ActA is a robust regulator of actin dep motility.

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64
Q

ActA structure.

A 
VCA domain (mimics N-WASP) so recruits Arp2/3. 
Polyproline repeats bind VASP (elongation and directionality). VASP cooperates with Arp2/3 - elongates F actin. 
Does not have GBD or PRD domains so no sequestration. 
Listeria
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65
Q

Listeria: actin in motility

A

Actin stays stationary, bacteria moves away.

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66
Q

Listeria: intracellular spread.

A

InlC, LLO, PlcB

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67
Q

Listeria: intracellular spread: InlC

A

Relaxes cortical tension by inhibiting host Tuba-WASP interactions (which provide the link between the membrane and the supporting cytoskeleton).

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68
Q

Listeria: intracellular spread: LLO

A

Lysis of 2nd vacuole.

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69
Q

Listeria: intracellular spread: PlcB

A

Closes protrusion.

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70
Q

Listeria invades which cells.

A

Transcytosis across M cells then into macrophages.

Also invades epithelial cells by zipper mechanism.

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71
Q

Zipper mechanism.

A

Contact and adherence, phagocytic cup formation and phagocytic cup closure and retraction.

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72
Q

Cells taken up by phagocytosis

A

Legionella, Mycobacterium, Salmonella, Coxiella.

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73
Q

Trigger mechanism

A

repression of secretion, interaction and secretion, formation of macropinocytic pocket, actin depolymerisation and closing of pocket.

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74
Q

Cells taken up by phagocytosis: legionella

A

Legionella; a parasite of amoebae and macrophages which phagocytose, so does not drive uptake itself.

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75
Q

Cells taken up by phagocytosis: mycobacterium

A

Complement receptors and complement opsonisation are main routes of uptake. But specific receptor unimportant.

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76
Q

Phagocytosis: salmonella

A

Also taken up by trigger mechanism. Requires induction of membrane ruffling requiring WAVE.

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77
Q

Phagocytosis: coxiella

A

Binds αvβ3 which is normally used in phagocytosis of apoptotic cells so does not induce inflammation.

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78
Q

Listeria - regulation of virulence genes

A

Temperature change to 37 degrees –> conformational change in mRNA of PrfA –> can be translated –> makes PrfA –> activates small chromosomal pathogenicity island.

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79
Q

Actin polymerisation cascade - spontaneous.

A

G actin nucleates –> unstable actin nucleus –> elongated to F actin

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80
Q

Actin polymerisation cascade - spontaneous. G actin nucleates –> unstable actin nucleus.

A

Inhibited by profilin

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81
Q

Actin polymerisation cascade - spontaneous. Unstable actin nucleus –> elongated to F actin.

A

Increased by profilin/ATP-actin. Elongation inhibited by capping protein CapZ.

82
Q

Actin polymerisation cascade - facilitated.

A

Attachment of Arp2/3 to a mother filament leads to branching. Profilin/ATP-actin used in elongation, with formin as capping protein.

83
Q

Orientation of actin filaments in comet tails.

A

Barbed ends towards bacteria. Propulsive force provided by polymerisation.

84
Q

ActA

A

Critical to virulence in the mouse model. Sufficient for comet formation. Activates Arp2/3.

85
Q

Actin turnover in comet tails

A

Cofilin, coronin and capping proteins are important. Acceleration of this maintains actin monomer pool.

86
Q

Actin comet tails formation overview.

A

Arp2/3 nucleates, VASP promotes speed and directionality, favours parallel filaments. Actinin stabilises. CapZ prevent nonproductive growth.

87
Q

Autophagy pathway

A

Targets cytosolic proteins and organelles to lysosomes, a key innate immune response against intracellular bacteria.
Phagophore –> autophagosome –> lysosome.

88
Q

Listeria and autophagy

A

LLO triggers by damaging vacuoles. ActA protects.

89
Q

Rho GTPases

A

Master regulators of the actin cytoskeleton. Recruit/activate N-WASP and WAVE.

90
Q

GEF

A

Guanine nucleotide exchange factor.

91
Q

GAP

A

GTPase activating protein.

92
Q

GDI

A

GTPase disassociation inhibitor.

93
Q

WAVE

A

Have VCA domain for Arp2/3 activation.

94
Q

Bacterial manipulation of Rho GTPases

A

Toxins tend to covalently modify, secreted effectors tend to mimic.

95
Q

Avoiding autophagy

A

Actin helps evade autophagy (motility or actin shel).

Phospholipases may degrade autophagosome.

96
Q

Yersinia cell entry

A

Zipper mechanism into epithelial cells from basolateral side via invasins.

97
Q

Invasins (Yersinia) - binding

A

Bind B integrins (usually mediate cell adhesion). Results in Rac1 remodelling and FAK recruitment. Src involved.

98
Q

Key Rho GTPases

A

RhoA - stimulates focal adhesion and stress fibres
Rac1 - induces lamellipodia and ruffling.
Cdc42 - produces filopodia.

99
Q

Invasins (Yersinia) - structure

A

Autotransport, not cleaved so anchored. D1, 2, 3 homo-oligomerise, D4, 5 bind integrins. Functionally mimics fibronectin (convergent evolution).

100
Q

Yersinia resisting macrophage uptake

A

Uses YOPs.

101
Q

Yersinia location

A

Inside epithelial cells, or in extracellular abscesses in Peyer’s patches.

102
Q

Inv locus Yersinia

A

Sufficient to convert E. Coli into bacteria which can penetrate cells. Codes for invasins
, critical for focal adhesion.

103
Q

Yersinia: importance of clustering in integrin binding.

A

Without clustering of integrins, no signalling occurs.

104
Q

Salmonella typhimuriusm functions of effectors in uptake

A

Interact with actin
Activate Rho GTPases by acting as GEFs
Activate Rho GTPases via inositol phosphate activity.

105
Q

Salmonella typhimurium functions of effectors in uptake: interaction with actin

A

SipC nucleates and bundles
SipA is a molecular staple preventing ADF mediated dissassembly.
SipA potentiates SipC.

106
Q

Salmonella typhimurium functions of effectors in uptake: activate Rho GTPases by acting as GEFs.

A

SopE activates Rac1, but SptP deactivates to restore actin cytoskeleton after invasion.

107
Q

Salmonella typhimurium functions of effectors in uptake: activating Rho GTPases via inositol phosphate activity.

A

SopB makes PIP3 –> membrane ruffling. Binds ARNO for Arf1 activation. Arf1 + Rac1 recruit WAVE and Arp2/3.

108
Q

Survival in vacuole: Salmonella induced filaments

A

Lysosomal membrane tubules induced by salmonella.

109
Q

Survival in vacuole: Salmonella induced filaments formation

A

SifA –> SKIP (a linker protein to kinesin) –> would go to peripheral distribution of lysosomes in cells. PipB2 also involved.

110
Q

Survival in vacuole: movement of SCVs to juxtanuclear region.

A

Near Golgi stacks.
Rab7 –> RILP –> dynactin –> dynein –> moves towards nucleus.
SseF and SSeG also involved.

111
Q

Types of filament induced by salmonella

A

SNX tubules (sorting nexin), SCAMP3 tubules and LAMP negative tubules.

112
Q

Salmonella - inducing cell death.

A

SlrP interacts with redox protein thioredoxin to cause apoptosis. SipB activates caspase 1 to cause macrophage death.

113
Q

Salmonella: inhibition of immune response

A

NFkB pathway and mRNA

114
Q

Salmonella: inhibition of immune response: NFkB pathway

A

Ubiquitin ligases IpaH and SspH1 are E3 ubiquitin ligases. Affects NFkB pathway and hence IL-8 production.

115
Q

Salmonella: inhibition of immune response: mRNA

A

SpvC irreversibly removes phosphates reducing cytokine mRNA

116
Q

Role of SPI-1 in salmonella uptake and cell infection.

A

Transcytosis across M cells.
Macrophage apoptosis and release of bacteria.
Uptake into cells.

117
Q

Role of SPI-2 in salmonella uptake and cell infection.

A

Growth inside macrophages.

118
Q

Salmonella divergence from E coli.

A

Acquisition of factors for intestinal colonisation - SPI-1
Acquisition of ability to cause systemic disease - SPI-2
Acquisition of ability to infect warm-blooded hosts.

119
Q

Salmonella regulation of virulence genes.

A

Mg++/Ca++ high in gut lumen.
PhoPQ inactive in high salt conditions –> transcriptional activators like HilA –> SPI1 active.
PhoPQ active –> SPI-1 repressed, SPI-2 activated.

120
Q

Salmonella effector translocation system

121
Q

SopB and SopE interactions in Salmonella

A

SopB generates PIP3, eventually recruits Arf1. SopE activates Rac1. Together they recruit WAVE.

122
Q

Understanding salmonella infection

A

In mouse: bacteria invade, escape and infect many more cells.
In cultured macrophages: invade and replicate intracellularly.
In humans: rarely escapes gut.

123
Q

Salmonella intracellular survival.

A

SPI-1 effectors –> early SCV formation.
Rabs are key to SCV formation and maturation.
Luminal environment triggers SPI-2 expression.
SPI-2 effectors maintain the vacuole, induce filaments and possibly have a role in egress.

124
Q

Positioning of SCV.

A

SseF and SseG maintain. Tether in a Golgi associated manner. Promote interactions with dynein.

125
Q

Salmonella typhi and paratyphi

A

Causes typhoid fever, a systemic disease.

126
Q

Non typhoidal salmonella

A

Salmonella enterica serovars typhimurium (mouse is natural host in which it causes typhoid).

127
Q

Number of SPIs

A

21, but 1 and 2 are the most studied

128
Q

SPI-1 effectors –> early SCV formation.

A

Consider for entry

SopB recruits Rab5.

129
Q

Salmonella: avoiding delivery of acid hydrolases

A

Normally: cation-independent mannose-6-phosphate receptor delivers lysosomal hydrolases from TGN to early endosomes.
SNX1 retrieves these vesicles back to the TGN.
SNX1 binds PI3P produced by SopB, so is localised to near the SCV to protect it.

130
Q

Sensing the luminal environment to express SPI-2 effectors.

A

SsrAB senses acidic environment and limitation of Pi. SsrB is the RR.
Causes transcription of T3SS and effectors.

131
Q

SCV maturation to intermediate SCV

A

Rab5 replaced by Rab7 (migration to perinuclear region).

SCV fuses with endosomes containing LAMP1 and vATPase.

132
Q

SPI-2 encodes

A

A type III secretion system.
A two component system.
Effector proteins.

133
Q

Interfering with NADPH oxidase - A. phagocytophilum

A

A. phagocytophilum interferes with assembly of NADPH oxidase subunits in inclusion membrane. and blocks activation of NADPH with phorbol myristic acetate.

134
Q

Interfering with NADPH oxidase - Listeria

A

Listeria ribosylate Rab5 to inactive to prevent NADPH oxidase mediated killing before escaping vacuole.

135
Q

Interfering with NADPH oxidase - Salmonella

A

Avoid recruitment.

136
Q

SifA

A

Required for vacuole integrity. Anchored to SCV membrane.
SifA –> recruits SKIP –> reroutes M6PR, hydrolases secreted into extracellular medium instead. Rab9 retrieves M6PR from the PM.

137
Q

Salmonella induced filament formation

A

PipB2 recruits kinesin.
SifA recruits SKIP, which activates kinesin.
Kinesin moves away from nucleus.
Generates Sifs, since SCV anchored by SseF/SseG.

138
Q

SCV movement to perinuclear region.

A

Rab7 binding RILP and then dynein/dynactin motor complex, salmonella containing vacuole moves towards nucleus.

139
Q

S. typhimurium broad host specificity

A

GtgE cleaves Rab32 which is necessary for lysosomal mediated death of S. typhi.

140
Q

Cytolethal typhoid toxin exocytosis

A

Salmonella.

Dependent on Rab27l

141
Q

Salmonella T3SS

A

Similar to flagella.

142
Q

Bacteria taken up by trigger mechanism

A

Salmonella, Shigella.

143
Q

Shigella invasion site

A

Transcytoses M cells.
Taken up by macrophages, induce apoptosis.
Invades epithelial cells from the basolateral side.

144
Q

Shigella general

A

Causes bacillary dysentry.

Shigella dysenteriae, Shigella flexneri, Shigella sonnei, Shigella boydii.

145
Q

Shigella regulation of invasive phenotype

A

The virulence plasmid is activated by VirF, a transcriptional regulator activated by physiological temperature. This causes transcription of VirF and VirB, which are also regulated by EnvZ-OmpR, CpxA-CpxR

146
Q

Shigella effectors

A

IpgD (like SopB), IpaA (binds vinculin), IpgB1 activates Rac1.
IpaC is part of translocon, but indirectly activates Rac1 and Cdc42.

147
Q

Escaping the vacuole: Shigella

A

Unknown mechanism. IpgD recruits Rab11. Unknown mechanism involves IpaB and IpaH. Possibly destabilising vacuole membrane.

148
Q

motility: Shigella

A

IcsA for actin, VirA to sever microtubules.

149
Q

IcsA structure and function.

A

Shigella. Identified in transposon mutagenesis.

Autotransported by Ctd domain. Ntd has glycine rich repeats. Binds N-WASP, activates Arp2/3.

150
Q

VirA: function.

A

Microtubule network hinders shigella motility. VirA is key to severance, controversy as to how - Yoshida suggested cysteine protease activity.

151
Q

Actin motility with branched actin

A

Listeria and Shigella.

Need ADF/cofilin, capZ and profilin.

152
Q

Shigella: inducing cell death

A

IpaB activates caspase 1 causing macrophage death.

153
Q

Shigella: inhibition of immune response: avoiding autophagy.

A

Actin based motility, actin shield and IcsB shield (competitively inhibits binding of autophagy related genes).

154
Q

Shigella: intracellular spread.

A

Poorly characterised. Cell-cell junctions are subverted.

155
Q

Mechanism of actin tails in Shigella

A

IcsA binds N-WASP. This binds Arp2/3 initially, and then feeds actin monomers onto the barbed end, propelling the bacterium away.

156
Q

Role of actinin

A

cross-links actin.

157
Q

Rickettsia motility

A

Doesn’t use Arp2/3. Sca2 mimics formin to to generate unbranched acting polymers.

158
Q

Determinants of vesicular transport

A

Membrane lipid composition
Membrane associated regulatory proteins
Lumenal environment.

159
Q

Cellular compartment definition

A

Lipid phosphoinositides

Rabs.

160
Q

Ways to deal with lysosomal pathway

A

1) Uncouple early from pathway (Chlamydia, Legionella)
2) Escape vacuole (Listeria, Shigella)
3) Prevent progression to lysosome (mycobacterium)
4) Survive progression to lysosome (Coxiella)

161
Q

LCV morphology

A

rER like. SldC promotes LCV-ER fusion.
Host proteins Sar1, ARF1 and Rab1 to recruit ER derived vesicles.
Recruit mitochondria.

162
Q

Legionella secretion system

A

T4SS, dot-icm.

163
Q

Number of legionella effector proteins

A

More than 300. Many interact with RhoGTPases or otherwise alter LCV morphology. Others provide nutrients. Examples: RalF, SldC, AnkB.

164
Q

T4SS

A

Core complex spans both inner and outer membrane.
Self-assembling.
Has cytoplasmic inner membrane subcomplex with 3 ATPases. Membrane anchors link to the core complex.

165
Q

Which bacteria use T4SSs?

A

H. Pylori, Brucella suis, Legionella pneumophila.

166
Q

RalF

A

Sequence homology to Arf1 GEF. Arf is important in Golgi-ER retrograde transport and formation of secretory vesicles. Legionella.

167
Q

AnkB

A

Recruits proteosome so that high levels of amino acids are generated by the LCV to provide nutrients. Legionella.

168
Q

Legionella uptake

A

Phagocytosis.

169
Q

Rab 1 control by Legionella.

A

SidM releases Rab1 from RabGDI. Recruited to LCVs. SidM converts to GTP bound form. Locks in constitutively active form by ampylation.
SidD deampylates later in infection, enabling deactivation by LepB.

170
Q

Mycobacterial phagosome maturation block.

A

LAM: ManLAM blocks Ca++ rise, preventing PI3P synthesis.
PI3P is dephosphorylated due to SapM.
Trehalose dimycolate.
Rab7 is converted to its inactive GDP bound form.

171
Q

EEA1

A

Tethering molecule essetial for fusion of early and late endosomes.

172
Q

Mycobacterium: inhibition of immune response

A

Binding of TLR2 leads to potent pro-inflammatory cascade, and inhibits IFNy induction and induction of antigen presenting genes.

173
Q

Mycobacterial cell wall

A

Lower segment

Upper segment includes LAM and PIM

174
Q

PIM stands for

A

Phosphatidylinositol mannosides.

175
Q

Granuloma progression

A

Shed Mtb cell wall components. Exocytosed. Induce macrophage differentiation to foam cells. Undergo necrosis.

176
Q

Mycobacterium secretion system

A

five ESX systems (T7SS)

177
Q

Mycobacterial phagosome

A

Highly dynamic. Contains some lysosomal markers. Accessible to early and recycling endosomes.
Indicators of trafficking arrest: retention of Rab5 . No EEA1, vATPase, Cathepsin D or Rab7.

178
Q

Mycobacterial damage to phagosomal membrane.

A

ESAT-6 and CFP-10 contribute to damage. Depend on each other for stability, secreted by ESX system.

179
Q

Mycobacterial acquisition of iron.

A

Early endosomes accessible due to Rab5 marker: acquires iron from these.

180
Q

Bacterial developmental transition on cell entry: Coxiella.

A

Small cell variant to large cell variant. Acidification = trigger.

181
Q

Coxiella burnetti avoidance of killing.

A

Uses T4SS like legionella, but not involved in avoiding lysosome as only expressed 8 hours post-infections.
Delays hydrolases.

182
Q

Roles of Coxiella effector proteins.

A

Promotion of CCV integrity.
Transcriptional modification.
Preventing apoptosis and cyt c release.
Proteasome mediated degradation for nutrients.

183
Q

Coxiella vacuolar expansion.

A

Induces autophagy –> giant vacuole via Cig2.
Requires recruitment of Rho GTPase and Rab1b – maintenance and acquisition of additional membranes. Expand from small to large coxiella containing vesicles.

184
Q

Intracellular bacteria rapidly escaping cell cytoplasm.2

A

Shigella, Listeria

185
Q

Intracellular bacteria remaining withing the membrane bound vesicle.

A

Salmonella, Legionella pneumophila, Brucella abortus or Chlamydia spp

186
Q

Intracellular survival

A

Bacterial developmental transition.
Stay in the vacuole?
Manipulating the host cell

187
Q

Manipulating the host cell

A

Bacteria containing compartment interacting with other compartments.
Altering host cell death
Inhibiting immune response.

188
Q

Exiting the host cell

A

Host cell death.
Exocytosis.
Intracellular spread.

189
Q

Inhibiting the immune response - mechanisms

A

Alter TLR binding
Alter NFkB
Alter cytokine mRNAs
Avoid autophagy.

190
Q

Bacteria using the zipper mechanism.

A

Listeria, Yersinia.

191
Q

Microorganisms and regulation of virulence

A

Listeria, PrfA.
Salmonella PhoPQ
Shigella VirF.

192
Q

Host cytoskeleton

A

Intracellular matrix that supports both shape and function.
Actin polymerisation
Rho GTPases
PIPs.

193
Q

Shigella disease

A

causes shigellosis in humans (and apes) = dysentery with imbalance of host regulation of inflammation due to bacterial —> one of the leading bacterial causes of diarrhoea worldwide with at least 100,000 deaths (mostly children in developing world
four serogroups: s. dysenteriae causes epidemics whereas s. flexneri and s. sonnei are endemic
faeco-oral transmission
invades colonic mucosa to cause destructive recto-colitis, fever, cramps and bloody stool

194
Q

Listeria disease.

A

food borne
causes gastroenteritis
invasive infection = listeriosis —> infection of the CNS — meningitis and brain accesses etc (only happens in immunocompromised, neonates, elderly, pregnant women and healthy persons who have ingested very large inoculum)

195
Q

Shigella virulence plasmid

A

has 220kb virulance plasmid that has mxi-spa locus that encodes T3SS and effector proteins Ipa-Ipg
VirF responds to pH, 37 degrees C, osmolarity and iron to induce VirB expression with in turn induces T3SS and effectors
also regulated by TCSs: osmotic stress (via EnvZ/OmpR) and pH (via CpxAR)

196
Q

Shigella: IpaB and C

A

bind cholesterol with high affinity and insert into membranes as translocon —> disrupt membrane to allow effector entry

197
Q

Shigella: IpgD

A

interacts with PIP2 to induces actin rearrangements

198
Q

Shigella: VirA

A

induces Rac1/Cdc42 dependent actin polymerisation and membrane ruffles

199
Q

Shigella: IpgB1 and B2

A

act as GEFs for RhoA and Rac respectively to promote remodelling

200
Q

Shigella: IpaA

A

mediates localised depolymerisation of actin via vinculin —> required to close the phagocytic cup

201
Q

SopB and SopE interactions in Salmonella

A

SopB generates PIP3, eventually recruits Arf1. SopE activates Rac1. Together they recruit WAVE.

ZZPathology undergraduate year 3, first term. (15 decks)

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