Channarong Rodkhum D.V.M., Ph.D. Department of Veterinary Microbiology Faculty of Veterinary Science Chulalongkorn University

Transcription

1 Course : Host-pathogen interactions ( ) Channarong Rodkhum D.V.M., Ph.D. Department of Veterinary Microbiology Faculty of Veterinary Science Chulalongkorn University

2 Outline Introduction Bacterial invasion mechanisms Consequences of invasion Bacterial survival and growth subsequent to invasion Regulation of virulence factors

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4 BACTERAIL DISEASE PROCESS Bacteria entry to host Adherence -Adhesins - Eating - Breathing - injected into host by an arthropod - trauma of the epithelium Colonization Invasion - Extracellular invasion; exotoxins and enzyme - Intracellular invasion; actin rearrangmemt Activation of host cells signalling cascade Clinical Disease

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6 INVASION MECHANISM Pathogen binding of host molecules to mediate invasion Once adhered to a host surface, some pathogen gain deeper access into the host to perpetuate the infection cycle. Extracellular invasion and intracellular invasion. The main type of host cell invaded by bacteria are epithelial cell and endothelial cells. Two strategies for intracellular invasion ; -Induced change in cell s cytoskeleton -Enter the cell without any involvement of cytoskeleton

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10 Two of the three typrs of filament that comprise the cytoskeleton of eukaryotic cells.

11 Temporary protrusions that can be formed by cell due to rearrangement of actin filaments. a) Filopodia b) Sheet-like extensions

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13 INVASION OF EPITHELIAL CELLS 1. Invasion involving actin rearrangements - inasion of Yersinia sp. - invasion of Listeria monocytogenes - invasion of Shigella sp. - invasion of Salmonella sp. 2. Invasion involving microtubules 3. Paracytosis ; bacteria penetrate the E-cadhedrins and occludin (cellular tight junctions).

14 Comparison of various invasion mechanisms [Finlay and Falkow, 1997]

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19 Invasion of intestinal epithelial cells by Yersinia sp.. Yersinia sp.can cross the intestinal epithelium by invading an M cell (a,b) and, as it can resist phagocytosis by associated macrophages (c,d), it can then invade an epithelial cell via its basolateral surface (d,e).

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21 Electron micrograph showing the membrane ruffling induced by Shigella flexneri (arrowed) on contacting an epithelial cell.

22 Invasionof epithelial cells by Shigella sp. Initial adhesion is, possibly, achieved by binding of LPS to an integrin (a,b) and this induces the injection of lpaa into the host cell (via a type III secretion system) and the secretion of ipaa complex (c). The latter is able to bind to both the α 5 β 1 - integrin and to the hyaruron receptor (CD44) and this results in extensive cytoskeletal rearrangement and pseudopod formation (d,e). The bacterium is taken up in vacuole (f) from which, like in L. monocytogenes, it escapes (g) and can move within the cell. The bacterium is able to invade a neighbouring cell via a cytoplasmic protrusion (h).

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25 Sequence of events occurring prior to, and following, adhesion of Shigella sp. to the epithelial cells. Adhesion (a) activates a type III secretion system (b) resulting in the secretion of effector molecules, some of which are injected into the host cell (C). This results in induction of signalling pathways and cytoskeletal rearrangements (d).

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27 Signalling pathways and cytoskeletal rearrangment involved in the uptake of Salmonella sp. by epithelial cells.

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29 Invasion of epithelial cells by Salmonella sp. Initial adhesion (a) is mediated by fimbriae, which then induce the formation of invasomes (b). Proteins are injected into the host cell via the secretions and these interfere with host cell signalling pathways and induce the cytoskeletal rearrangments essential for engulfment of the bacterium (c). The bacterium is taken up by the cell and resides in a vacuole (d).

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31 INVASION OF ENDOTHELIAL CELLS 1. Inasion of Neisseria meninggitidis 2. Invasion of Listeria monocytogenes 3. Invasion of Citrobacter freundii 4. Invasion of Bartonella henselae 5. Invasion of β-hemolytic Streptococci 6. Invasion of Streptococcus pneumoniae

32 CONSEQUENCES OF INVASION Effect on host cells : 1. Cytokine release 2. Proataglandin release 3. The expression of adhesion molecules and neutrophil adhesion 4. Cell death (apoptosis) 5. Synthesis of tissue factor ; - Transmembrane protein produced by endothelial cells in response to variety of stimuli. - Resulting in production of fibrin which coat the cells. - Vegetative endocarditis of heart valves)

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34 CONSEQUENCES OF INVASION Effect on bacteria : Up- or down-regulate of bacterial genes.

35 THANK YOU