Cancer Listeria and exploitation of actin cytoskeleton Flashcards Preview

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Flashcards in Cancer Listeria and exploitation of actin cytoskeleton Deck (15)
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1

Virulence mechanism in Listeria

Exploits eukaryotic cells' actin cytoskeleton to produce 'comet tails', which is uses to invade neighbouring cells intracellularly

2

Summary of comet tail propulsion

Actin strands stay in one place (due to alpha actinin/fimbrin cross linking proteins)
Increased assembly of actin filaments at bacterial end pushes bacteria forward as acting filaments from other end are disassembled

3

Protein on Listeria necessary for comet tail production and location

ActA dimer

On one pole of bacterium

4

Summarise ActA's role in comet tail formation

ActA has a proline-rich region to which VASP (normal cell protein necessary for cytoskeleton pros) binds. VASP recruits Arp2/3, which act as nucleation sites. Profilin ensures good supply of ATP and G-actin to ActA for preferential assembly in bacterial direction

5

Proteins involved in cross linking actin in this arrangement

alpha actinin and fimbrin

6

Proteins involved in capping F-actin chains

cofilin

7

Describe how Listeria enters eukaryoic cells

Listeria bind to the outside of cells, via one of the cell surface adhesion molecules (E-cadherin) ->
internalisation by normal endocytosis or phagocytosis ->
acidic compartment->
lysin protein is
produced which breaks down the membrane of compartment->
Listeria enters cytoplasm

8

Why is Listeria's poropulsion mechanism important in pathophysiology?
Give examples

Listeria can cross bodily compartments (without there being injury to them) eg BBB, placenta

9

Mechanism of transport of Listeria through the blood

Intracellular within macrophages and monocytes

10

Common target tissues of Listeria infection

liver
brain by crossing BBB -> meningitis
syncytiotrophoblasts -> vertical tranismission to foetus

11

Route of entry of Listeria

GI tract

12

Immune response against Listeria
+ reason

Cell-mediated (unusual for bacteria)

Intracellular in host cells so immune to Ab and complement activation

13

Susceptible individuals to Listeria

Those with impaired cell-mediated immune respone/T lymphocytes:
very young
very old
pregnant women
HIV+/AIDS
immunosuppressed individuals eg transplant pts

14

Common way Listeria infects humans

Lives in soil -> uncooked fruit + veg
In unpasteurised products eg soft cheese, pate

15

Recommendations for at -risk groups

Don't eat unpasturised products