OT: Bacterial pathogenesis: EXPLOITING THE HOST!!!

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Research Highlight

Nature Reviews Microbiology 4, 492-493 (July 2006) | doi:10.1038/nrmicro1451

Bacterial pathogenesis: Exploiting the host

Amoils

The phosphatidylinositol 3-kinase (PI3K) pathway has crucial roles in many

eukaryotic cellular processes, including membrane trafficking and

receptor-mediated and stress-related signal transduction. Two papers

recently published in PLoS Pathogens describe how two different

intracellular pathogens interact with and exploit this fundamental cellular

pathway.

Ojcius, Philippe Verbeke, Toni Darville, Georg Häcker and colleagues

show that Chlamydia trachomatis co-opts the PI3K pathway to prevent

host-cell apoptosis. C. trachomatis replicates in an intracellular vacuole,

known as an inclusion, and inhibits host-cell death in part by promoting the

degradation of pro-apoptotic BH3-only proteins such as BAD. By analysing C.

trachomatis-infected epithelial cells in the presence or absence of

functional PI3K, Ojcius and colleagues revealed that functional PI3K

protects C. trachomatis-infected cells from apoptosis. Activation of PI3K

results in the phosphorylation and activation of the pro-survival protein

AKT, which phosphorylates BAD. Phosphorylated BAD is retained at the

Chlamydia inclusion by binding to the 14-3-3 cellular adaptor protein, which

itself binds to the chlamydial inclusion protein IncG. By sequestering

pro-apoptotic BAD away from the mitochondria, untimely apoptosis of the host

cell is prevented.

The interaction of Legionella pneumophila with phosphatidylinositol lipids

was investigated by Hubert Hilbi and colleagues using a Dictyostelium

discoideum model of L. pneumophila infection. L. pneumophila replicates

within a membrane-bound compartment, the Legionella-containing vacuole

(LCV), which is formed by fusion with endoplasmic-reticulum-derived

secretory vesicles and evolves from a 'tight vacuole' into a 'spacious

vacuole'. The formation of the LCV requires the intracellular

multiplication/defective organelle trafficking (Icm/Dot) type IV secretion

system. The authors showed that functional PI3Ks restrict intracellular

growth of L. pneumophila and promote the transition of the LCV into a

spacious vacuole, implicating the PI3K pathway in the trafficking and

evolution of the LCV. SidC, a protein secreted by Icm/Dot, is found on the

LCV and interacts in vitro with phosphatidylinositol(4) phosphate (PI(4)P),

a PI3K substrate that is found in the trans-Golgi apparatus and on the LCV

membrane.

These results provide evidence that L. pneumophila uses membrane & shy;bound

PI(4)P to anchor SidC and possibly other secreted proteins to the LCV. The

authors suggest that this interaction could facilitate the formation of a

replicative vacuole, and promote the trafficking and exit of L. pneumophila

from host cells.

Links

DATABASES

UniProtKB

IncG

SidC

References and links

ORIGINAL RESEARCH PAPERS

Verbeke, P. et al. Recruitment of BAD by the Chlamydia trachomatis vacuole

correlates with host-cell survival. PLoS Pathogens 2, e45 (2006)

Weber, S. S. et al. Legionella pneumophila exploits PI(4)P to anchor

secreted effector proteins to the replicative vacuole. PLoS Pathogens 2, e46

(2006)