Cancer Listeria and exploitation of actin cytoskeleton

Question 1

Virulence mechanism in Listeria

Answer 1

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

Question 2

Summary of comet tail propulsion

Answer 2

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

Question 3

Protein on Listeria necessary for comet tail production and location

Answer 3

ActA dimer

On one pole of bacterium

Question 4

Summarise ActA’s role in comet tail formation

Answer 4

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

Question 5

Proteins involved in cross linking actin in this arrangement

Answer 5

alpha actinin and fimbrin

Question 6

Proteins involved in capping F-actin chains

Answer 6

cofilin

Question 7

Describe how Listeria enters eukaryoic cells

Answer 7

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

Question 8

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

Answer 8

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

Question 9

Mechanism of transport of Listeria through the blood

Answer 9

Intracellular within macrophages and monocytes

Question 10

Common target tissues of Listeria infection

Answer 10

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

Question 11

Route of entry of Listeria

Answer 11

GI tract

Question 12

Immune response against Listeria

+ reason

Answer 12

Cell-mediated (unusual for bacteria)

Intracellular in host cells so immune to Ab and complement activation

Question 13

Susceptible individuals to Listeria

Answer 13

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

Question 14

Common way Listeria infects humans

Answer 14

Lives in soil -> uncooked fruit + veg

In unpasteurised products eg soft cheese, pate

Question 15

Recommendations for at -risk groups

Answer 15

Don’t eat unpasturised products