Manipulation of host membranes by bacterial effectors

Ham, Hyeilin; Sreelatha, Anju; Orth, Kim

doi:10.1038/nrmicro2602

Cited by 124 publications

(115 citation statements)

References 99 publications

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“…Although comprising less than 10% of total phospholipids, PIs are pivotal cellular regulators and play essential roles in a broad spectrum of cellular processes including defining intracellular organelle identity, cell signaling, proliferation, cytoskeleton organization, and membrane trafficking (9)(10)(11). Interference of the temporal and spatial distribution of intracellular PIs often leads to abnormal cellular functions, which has been capitalized by virulent invaders (12,13). Bacterial pathogens have evolved a variety of mechanisms to subvert PI metabolism in host cells.…”

mentioning

confidence: 99%

“…Modulation of host PI metabolism by Legionella is important for the establishment of the Legionella-containing vacuole (LCV) within which the bacterium replicates (8,12,13). It has been suggested that PI(4)P is enriched on the LCV membrane, which among other functions, anchors effectors such as SidM/DrrA, SidC, and SdcA to promote the recruitment and fusion of the endoplasmic reticulum derived vesicles with the LCV (18,19).…”

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confidence: 99%

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Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase

Hsu

Zhu

Brennan

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

104

113

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Legionella pneumophila is an opportunistic intracellular pathogen that causes sporadic and epidemic cases of Legionnaires' disease. Emerging data suggest that Legionella infection involves the subversion of host phosphoinositide (PI) metabolism. However, how this bacterium actively manipulates PI lipids to benefit its infection is still an enigma. Here, we report that the L. pneumophila virulence factor SidF is a phosphatidylinositol polyphosphate 3-phosphatase that specifically hydrolyzes the D3 phosphate of PI(3,4)P 2 and PI(3,4,5)P 3 . This activity is necessary for anchoring of PI(4)Pbinding effectors to bacterial phagosomes. Crystal structures of SidF and its complex with its substrate PI(3,4)P 2 reveal striking conformational rearrangement of residues at the catalytic site to form a cationic pocket that specifically accommodates the D4 phosphate group of the substrate. Thus, our findings unveil a unique Legionella PI phosphatase essential for the establishment of lipid identity of bacterial phagosomes.phosphoinositide signaling | phagocytosis | membrane trafficking | type IV secretion system | virulence factor

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confidence: 99%

mentioning

confidence: 99%

Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase

Hsu

Zhu

Brennan

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

104

113

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“…In their active state, small GTPases interact with downstream effectors that promote membrane transport. Not surprisingly, many vacuolar pathogens regulate the recruitment and activation state of host cell GTPases to alter the trafficking of their vacuole [1,14]. Salmonella enterica Typhimurium initially recruits Rab5, a marker of early endosomes to its vacuole [15,16].…”

Section: Role Of Small Gtpases In Vacuole Stabilitymentioning

confidence: 99%

Maintenance of vacuole integrity by bacterial pathogens

Creasey

Isberg²

2014

Current Opinion in Microbiology

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Many intracellular bacterial pathogens reside within a membrane-bound compartment. The biogenesis of these vacuolar compartments is complex, involving subversion of host cell secretory pathways by bacterial proteins. In recent years it has become clear that disruption of vacuole biogenesis may result in membrane rupture and escape of bacteria into the host cell cytosol. Correct modulation of the host cell cytoskeleton, signalling molecules such as small GTPases and the lipids of the vacuole membrane have all been shown to be critical in the maintenance of vacuole integrity. Increasing evidence suggests that vacuole rupture may result from aberrant mechanical forces exerted on the vacuole, possibly due to a defect in vacuole expansion.

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“…In common with many other intracellular pathogens, rickettsiae utilize a ''zipper'' mechanism to mediate their cellular internalization (Ham et al, 2011). Rickettsiae exploit the cytoskeleton to enter and spread within the host cell.…”

Section: Isolationmentioning

confidence: 99%

Update on Rickettsioses in Slovakia

Sekeyová¹,

Socolovschi²,

Špitalská³

et al. 2013

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Summary. -The reported incidence of vector-borne diseases including various cases of Rickettsioses in humans is increasing due to a combination of climatic and social factors, escalating the opportunities for contact between people and ticks, fleas or lice. Many of the emerging infectious diseases currently challenging human health in Europe are transmitted by ticks which normally feed on domestic or wild animals. Each Rickettsia spp. has one or several tick vectors, and their geographical distribution varies according to geographical conditions; e.g.; altitude or temperature, which is gradually changing due to a global warming. Evidence of Rickettsia spp. particularly of a newly discovered species is a strong indication that a great number of diseases may be caused by so far undetected or unrecognized organisms. Their diagnosis relies mostly on rare "spot like" cooperation of clinicians with scientists, the members of the working groups that are devoted to the scientific studies of the corresponding research areas. The clinical picture of the disease caused by rickettsiae varies significantly from flu like symptoms to severe fatal outcomes, reflecting the various factors, e.g. a variability of virulence of rickettsial species due to cell invasion, dissemination of rickettsiae, genomics, immune response of an infected organism, or a tricky impact of a treatment. Several major reviews on rickettsioses have been previously published, e.g. in 1997(Parola et al., 2005, and in 2011 (Botelho-Nevers and Raoult, 2011). In this work we intend to present a short historical overview and to describe new trends in research studies of rickettsiology. The main focus will be on rickettsioses affecting Europe΄s population.

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Manipulation of host membranes by bacterial effectors

Cited by 124 publications

References 99 publications

Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase

Structural basis for substrate recognition by a unique Legionella phosphoinositide phosphatase

Maintenance of vacuole integrity by bacterial pathogens

Update on Rickettsioses in Slovakia

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