Publication Date:
2016-04-12
Description:
Upon entry into host cells, intracellular bacterial pathogens establish a variety of replicative niches. Although some remodel phagosomes, others rapidly escape into the cytosol of infected cells. Little is currently known regarding how professional intracytoplasmic pathogens, includingShigella, mediate phagosomal escape.Shigella,like many other Gram-negative bacterial pathogens, uses a type III secretion system to deliver multiple proteins, referred to as effectors, into host cells. Here, using an innovative reductionist-based approach, we demonstrate that the introduction of a functionalShigellatype III secretion system, but none of its effectors, into a laboratory strain ofEscherichia coliis sufficient to promote the efficient vacuole lysis and escape of the modified bacteria into the cytosol of epithelial cells. This establishes for the first time, to our knowledge, a direct physiologic role for theShigellatype III secretion apparatus (T3SA) in mediating phagosomal escape. Furthermore, although protein components of the T3SA share a moderate degree of structural and functional conservation across bacterial species, we show that vacuole lysis is not a common feature of T3SA, as an effectorless strain ofYersiniaremains confined to phagosomes. Additionally, by exploiting the functional interchangeability of the translocator components of the T3SA ofShigella,Salmonella, andChromobacterium, we demonstrate that a single protein component of the T3SA translocon—ShigellaIpaC,SalmonellaSipC, orChromobacteriumCipC—determines the fate of intracellular pathogens within both epithelial cells and macrophages. Thus, these findings have identified a likely paradigm by which the replicative niche of many intracellular bacterial pathogens is established.
Print ISSN:
0027-8424
Electronic ISSN:
1091-6490
Topics:
Biology
,
Medicine
,
Natural Sciences in General
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