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Immunology > Lecture 15: Bacteria and Invasion > Flashcards

Lecture 15: Bacteria and Invasion Flashcards

1
Q

What is the invasion for bacterial pathogens?

A

Ability of bacteria to reach a sterile site in the host

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2
Q

What is invasion of intracellular bacteria?

A

Active process managed by bacteria to enter into non-phagocytic eukaryotic cell

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3
Q

Meningitis

A

Neisseria meningitidis

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4
Q

Pneumonia and tuberculosis

A

Mycoplasma pneumoniae Legionella pneumophila Pseudomonas aeruginosa

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5
Q

Dysentery and diarrhoea

A

Shigella spp. Salmonella spp. Yersinia enterocolitica Listeria monocytogenes.

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6
Q

Urinary tract infection

A

Uropathogene Escherichia coli (UPEC)

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7
Q

Systemic infection

A

Staphylococcus aureus

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8
Q

What are the advantages to bacteria invading?

A

Avoid competitors Avoid immune response Cross mucosal barrier Multiplication and dispersal in the host Gain access to nutrients

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9
Q

What are the challenges to bacteria invasion?

A

How to enter into non-phagocytic cells Must survive defenses at new site, within the cell I.e. avoid or survive within the lysosomal and phagosomal environment

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10
Q

Cell invasion system: triggering an

A

Bacteria inject virulence factors directly into host cell cytoplasm to activate their own uptake by cell Bacteria only weakly adhere to cell Bacteria force the cell to extend local protrusion that engulf the bacterium (Rho GTPases) Type 3 secretion system-dependent

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11
Q

Cell invasion system: Zippering

A

Entry mediated by high affinity binding of a pathogen surface protein with a transmembrane receptor on host cell. Tight envelopment of pathogen by host cell membrane and uptake of bacteria

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12
Q

What is an example of trigger mechanism?

A

Salmonella spp.

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13
Q

What is an example of zipper mechanism?

A

Listeria monocytogenes

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14
Q

What is a systemic life-threatening infection?

A

Salmonella enterica serovar Typhi (and Paratyphi)

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15
Q

How many cases and death for typhoid fever?

A

20 million cases per year. 200.000 deaths (low and middle income countries)

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16
Q

What is non-typhoidal salmonella (NTS)?

A

Serovar Typhimurium and Enteritidis

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17
Q

How many cases and deaths of Gastroenteritis and Bacteremia?

A

90 million cases annually 150.000 death annually (high-income countries)

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18
Q

Who does Gastroenteritis and bacteremia affect?

A

Immunocompromised and poor economic countries

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19
Q

What is the life cycle of salmonella?

A
  1. Entry through M cells 2. Entry into macrophage survival/ multiplication Apoptosis. Initiation of inflammation. 3. Invasion of epithelial cell multiplication. B1. Entry through epithelial cells survival/multiplication. C.1. Entry through dendritic cells systemic dissemination
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20
Q

What are trigger mechanisms characterised by?

A

Massive ruffles Clustering of F actin beneath the entering bacteria

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21
Q

What is the function of SPI-1: cell invasion?

A

Expression in lumen Stimulation of pro-inflammatory response

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22
Q

What is the function of SPI-2: survival and replication inside cells?

A

Expressed inside host cells Formation of salmonella containing vacuoles (SCV) Prevention of endocytic traffic and phagosome maturation

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23
Q

SPI-1

A

Cytoskeletal rearrangement Triggering of Cell entry Apoptosis Loss of electrolytes Inflammation

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24
Q

SPI-2

A

Systemic spread Proliferation in host organs Intracellular Proliferation

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25
Q

What are the molecular switch that regulates several cellular processes?

A

Growth Differentiation Cytoskeletal organisation Trafficking

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26
Q

What is RAS involved in?

A

Growth survival

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27
Q

What is RAN involved in?

A

Nuclear transport

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28
Q

What is SAR1/ARF involved in?

A

Vesicle transport

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29
Q

What is Rho involved in?

A

Cytoskeleton dynamic

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30
Q

What are the three main small Rho GTPases?

A

RhoA, Rac, Cdc42

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31
Q

What regulates actin cytoskeleton organisation?

A

Rho GTPases

32
Q

What are some examples of actin cytoskeleton organisation?

A

Cell shape, motility, gene expression, cell-cell adhesion.

33
Q

What is an example of RhoA?

A

Stress fibers

34
Q

What is an example of RAC1?

A

Lamellipodia, membrane ruffles

35
Q

What is an example of Cdc42?

A

Filopodia

36
Q

What are SopE and SopE2?

A

GEF like molecules. Bind and activate small GTPases Cdc42 and Rac acting as a GEF. Induce membrane ruffling: promote cell entry. Rac activation essential for invasion

37
Q

What does GEF stand for?

A

Guanine nucleotide exchange factor

38
Q

What is SopB?

A

Phosphatidylinositol phosphatase

39
Q

What does sopB do?

A

Act on host phospholipid at membrane cell. Stimulate SH-3 containing GEF for RhoG. RhoG Activation: actin rearrangement and membrane ruffling

40
Q

What is SipA?

A

Stabilises actin filament by inhibiting their depolymerisation by cellular Actin binding proteins

41
Q

What is Fimbrin?

A

Actin cross linking protein important in formation of Filipodia

42
Q

What forms the translocon/pore for secretion of other effector into host cell?

A

SipB and SipC

43
Q

What does SipC initiate?

A

Actin nucleation via C- and N- terminal cytoplasmic domain

44
Q

What does C term nucleate?

A

Assembly of actin filaments

45
Q

What does N term induce?

A

Bundling of actin filament

46
Q

What does salmonella inject?

A

SptP

47
Q

What is SptP?

A

GAP - inhibitor of small GTPases

48
Q

What does SptP inhibit?

A

Rac and Cdc42 activated by sopE

49
Q

Where does salmonella replicate?

A

Salmonella containing vacuole (SCV)

50
Q

What bacterial genes (SPU-2) are required for the survival and replication?

A

SifA SseJ

51
Q

In epithelial cells, where are salmonella found?

A

Birth free in the cytoplasm and enclosed in SCV

52
Q

What is Listeria monocytogenes?

A

Food borne disease but can be transmitted to fetus by mother

53
Q

Where is Listeria monocytogenes most common ?

A

Immunocompromised. Newborns (meningitis). Pregnant women. (Miscarriages - still birth).

54
Q

What can Listeria monocytogenes cross?

A

Mucosal barriers and infect a wide range of cell types including macrophages

55
Q

What is the Listeria monocytogenes invasion gene?

A

inlAB

56
Q

How was internaline A and B genes identified?

A

Screening a library of transposon mutants of L.monocytogenes for loss of invasion of Caco-2 cells

57
Q

Where does Internalin A (InIA) bind?

A

Cell surface receptor E-Cadherin

58
Q

Where does Internalin B (InIB) bind?

A

Cell surface receptor Met

59
Q

What is E-Cadherin?

A

Transmembrane protein belongs to a large family of cell-cell adhesion molecules

60
Q

What is E-Cadherin required for?

A

Correct formation of adherens junctions between epithelial cells

61
Q

What does E-Catherine form with alpha and beta catenins?

A

Large complex

62
Q

Zipper mechanism InIA-dependent

A

Listeria invade enterocyte via basolateral domain or via cell extrusion area Internalisation via a interaction between InIA and E-Cadherin - subvert signalisation produced by this protein

63
Q

What is zipper mechanism InIA dependent required for?

A

Crossing of intestinal and placenta-foetus barriers

64
Q

What is Met?

A

Receptor for hepatocyte growth factor

65
Q

Met receptor for Internalin B

A

Protein tyrosine kinase

66
Q

What does binding of HGF to Met activate?

A

Cellular survival and proliferation signal Induces cytoskeletal rearrangement

67
Q

How is the receptor of Met degraded

A

HGF induce ubiquitination and internalisation by clathrin-mediated endocytosis mechanism

68
Q

What is the mechanism of InIB dependent?

A

InIB binds Met receptor and mimics HGF InIB induces autophosphorylation and ubiquitination of Met (endocytic machinery). Met several adaptors lead to activation of class IA PI3K and Rac1GTPases

69
Q

What is internalisation if InIB dependent mechanism depend on?

A

Actin and Arp2/3 complex. Involve Cdc42-Rac1 [effectors: N-WASP and WAVE]

70
Q

What is InIA?

A

Intestinal barrier

71
Q

What is InIA + InIB?

A

Placental barrier

72
Q

What is Actin based motility: ActA?

A

Listeria expresses it which acts like WASP proteins and recruit actin and Ena/VASp host cell proteins

73
Q

What does Actin based motility allow?

A

Intracellular motility Intercellular spreading via Actin polymerisation

74
Q

What is Autophagy?

A

Process used by eukaryotic cell to recycle old or damaged components in response to cellular damage or stress

75
Q

What is Xenophagy/autophagy?

A

Use of autophagy against invading pathogen: detect and destroy intracellular free bacteria

76
Q

What is the process of Autophagy?

A

Intracellular organelle or pathogen. Isolation-membrane. Autophagosome. Autolysosome degradation

77
Q

How does ActA protect/mask bacteria against Autophagy recognition?

A

Recruit actin and Ena/VASP host cells

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