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Flashcards in lecture 15 Deck (60):
1

what is Invasion for bacterial pathogens

Ability of bacteria to reach a sterile site in the host

2

what is Invasion for intracellular bacteria

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

3

what are some Advantages Why bacteria invade?

-To avoid competitors
- Avoid immune response
- To cross mucosal barrier
- Multiplication and dispersal in the host - gain access to nutrients

4

challenges of bacteria invasion

- 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

5

what are the two invasion systems-

Triggering and zippering

6

what happens in Triggering

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

7

what happens in zippering

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

8

what is Salmonella enterica serovar Typhi (and Paratyphi )

systemic life-threatening infection

9

example of Salmonella enterica serovar Typhi (and Paratyphi )

Typhoid fever

10

how many cases of Typhoid fever per year

More than 20 millions cases per year

11

how many people died from Typhoid fever

200.000 deaths (low and middle income countries (LMICs)

12

example of – Non-typhoidal Salmonella (NTS), serovar Typhimurium and Enteritidis

Gastroenteritis and bacteremia

13

how many cases of Gastroenteritis and bacteremia

: More than 90 million cases annually

14

who is at risk of gastroenteritis and bacteremia

immunocompromised and in poor economic countries

15

how many people die from gastroenteritis and bacteremia

150.000 death annually. (high-income countries (HICs)

16

what is the cycle of salmonella

A.1- Entry through M cells
2- Entry into macrophage Survival/ multiplication Apoptosis
Intitiation of inflammation
3- Invasion of epithelial cell Multiplication
B.1- Entry through epithelial cells Survival/ multiplication
C.1- Entry through dendritic cells Systemic dissemination

17

what is Trigger mechanism characterized by

massive ruffles and clustering of F-actin beneath the entering bacteria

18

what are the two distinct T3SS that salmonella encode

SPI-1:
SPI-2

19

what is the Functions SPI-1

- cell invasion
- Expressed in lumen
- stimulation of proinflammatory response

20

what is the Functions SPI-2:

- survival and replication inside cells
- Expressed inside host cells
- Formation of Salmonella containing vacuole (SCV)
- Prevention of endocytic traffic and phagosome maturation

21

what are Small GTP binding proteins or small GTPases

Molecular switches that regulate several cellular processes: Growth, differentiation, cytoskeletal organization, trafficking.

22

what are the Three main small Rho GTPases

RhoA, Rac, Cdc42

23

what do RhoA, Rac, Cdc42 regulate?

Regulate actin cytoskeleton organization:
- cell shape, motility, cytokinesis, gene expression, cell-cell adhesion...

24

what are SopE and SopE2

GEF like molecules

25

what do SopE and SopE2 bind and activate

Bind and activate small GTPases Cdc42 and Rac acting as a GEF (guanine nucleotide exchange factor)

26

function of sopE and SopE2

Induce membrane ruffling which promotes cell entry - Rac activation essential for invasion

27

what is SopB

phosphatidylinositol phosphatase
• Small GTPase

28

where does SopB act

Acts on host phospholipids at the membrane cell

29

what does sopB stimulate?

Stimulates SH-3 containing GEF (SGEF) for RhoG - RhoG activation induces actin rearragements and membrane ruffling

30

function of SipA:

stabilizes the actin filaments by inhibiting their depolymerization by cellular Actin binding proteins (ABPs

31

what do SipB and SipC form

SipB and SipC form the translocon retion of the other effectors into the host cell

32

what does • SipC do

SipC also initiates actin nucleation via its C-and N-terminal cytoplasmic domains. C-term nucleates the assembly of actin filaments, N-term induces bundling of actin filaments

33

what happens Following internalization

Following internalization, Salmonella needs to restore the normal
cellular architecture, i.e. stop ruffling

34

what do Salmonella inject

Salmonella inject SptP: SptP is a GAP (inhibitor of small GTPases) • SptP is degraded later than SopE/E2 into infected cells

35

what does SptP inhibit?

inhibits both Rac and Cdc42 activated by SopE

36

where dos Salmonella replicate?

Salmonella containing vacuole (SCV):

37

where does it Redirects the fate of this compartment

Redirects the fate of this compartment away form the normal phagosomal pathway

38

.what are Numerous bacterial genes (SPI-2) required for

Numerous bacterial genes (SPI-2) are required for the survival and replication: SifA, SseJ

39

where is Salmonella found

both free in the cytoplasm and enclosed in SCV

40

Zipper mechanism- Listeria monocytogenes --> how is Food borne disease transmitted?

transmitted to the fetus by the mother

41

in humans who is most likely to get a disease

immunocompromised, newborns (meningitis), pregnant women (miscarriages- stillbirth)

42

where do Zipper mechanism- Listeria monocytogenes / food borne diseases cross and what do they affect

Cross mucosal barriers and infect a wide range of cell types including macrophages

43

Listeria monocytogenes invasion genes (inlAB) --> how was Internaline A and B genes identified?

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

44

what Proteins used are for entry

Internalin A (InlA)
Internalin B (InlB)

45

where does Internalin A (InlA) bind?

binds to cell surface receptor E-Cadherin

46

where does Internalin B (InlB) bind?

binds to cell surface receptor Met

47

in the Zipper mechanism in enterocytes what is : E-cadherin receptor for

Internalin A

48

what is E-cadherin

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

49

what are • E-cadherin needed for

are required for the correct formation of adherens junctions between epithelial cells.

50

what do • E-cadherin form complex with

E-cadherin form a large complex with a and b catenins.

51

what is the Zipper mechanisms InIA-dependent

• Listeria invade enterocyte via basolateral domain or via cell extrusion area
• Internalisation via a interaction between InternalinA (InlA) and E-cadherin and subvert signalisation induced by this protein
• Required for crossing of intestinal and placenta-foetus barriers

52

what is Zipper mechanism Met receptor for Internalin B

• Met : receptor for hepatocyte growth factor
• Protein tyrosine kinase
• Binding of HGF to Met activates cellular survival and proliferation signal and it induces cytoskeleton rearrangements
• HGF induce a ubiquitination and internalisation by a clathrin mediated endocytosis mechanism leading to degradation of the receptor.

53

what is Zipper mechanism InlB-dependent

InlB binds Met receptor and mimics HGF
• InlB induces autophosphorylation and ubiquitination of Met and take advantage of endocytic machinery
• Met several adaptors leading to activation of class IA PI3K and Rac1GTPases
• Internalisation is dependant on actin and Arp2/3 complex and involves Cdc42-Rac1 and their effectors N-WASP and WAVE

54

where are both of these used

Whilst both are used in the intestinal barrier A is most important. Both are essential for crossing the placental barrier. Research as to meningitis is not confirmed yet

55

Actin based motility : ActA
what does Listeria expresses

Listeria expresses ActA which acts like WASP proteins a

56

what does Listeria recruit?

actin and Ena/VASP host cells proteins

57

what does this allow for

allowing intracellular motility and intercellular spreading via actin polymerisation

58

what is Autophagy

process used by eukaryotic cells to recycle old or damaged components in
response to cellular damage or stress

59

what is Xenophagy/autophagy

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

60

what does ActA and whats its function

ActA recruits actin and Ena/VASP host cells protecting/masking the bacteria against autophagic recognition