Abstract
Shigella is a Gram-negative bacterial pathogen, which causes bacillary dysentery in humans. A crucial step of Shigella infection is its invasion of epithelial cells. Using a type III secretion system, Shigella injects several bacterial effectors ultimately leading to bacterial internalization within a vacuole. Then, Shigella escapes rapidly from the vacuole, it replicates within the cytosol and spreads from cell-to-cell. The molecular mechanism of vacuolar rupture used by Shigella has been studied in some detail during the recent years and new paradigms are emerging about the underlying molecular events. For decades, bacterial effector proteins were portrayed as main actors inducing vacuolar rupture. This includes the effector/translocators IpaB and IpaC. More recently, this has been challenged and an implication of the host cell in the process of vacuolar rupture has been put forward. This includes the bacterial subversion of host trafficking regulators, such as the Rab GTPase Rab11. The involvement of the host in determining bacterial vacuolar integrity has also been found for other bacterial pathogens, particularly for Salmonella. Here, we will discuss our current view of host factor and pathogen effector implications during Shigella vacuolar rupture and the steps leading to it.
Highlights
Upon type 3 secretion system (T3SS)-triggered internalization into epithelial cells, Shigella rapidly ruptures its vacuolar membrane to reach the host cytosol for proliferation and cell-to-cell spread
Despite the importance of vacuolar rupture for intracellular bacterial proliferation and propagation, the underlying molecular mechanism has only recently been studied in more detail, and we still lack a precise understanding of the overall processes leading to and determining it (Ray et al, 2009, 2010; Carayol and Tran Van Nhieu, 2013a)
We will give an overview on the formation of the Shigella-containing vacuole, we will discuss the involvment of bacterial and host factors in the destablization of the vacuolar membrane, and we will compare it with vacuolar rupture by other bacterial pathogens
Summary
Upon type 3 secretion system (T3SS)-triggered internalization into epithelial cells, Shigella rapidly ruptures its vacuolar membrane to reach the host cytosol for proliferation and cell-to-cell spread. Work implicated the T3SS effectors/translocators IpaB and IpaC in vacuolar rupture due to their ability to insert into the host cell membrane for the delivery of bacterial effectors These studies demonstrated that IpaB and IpaC can disrupt lipid vesicles (liposomes) in vitro and are required for contact-mediated hemolysis by Shigella as well as bacterial phagosomal escape in macrophages (High et al, 1992; Ménard et al, 1993; De Geyter et al, 1997; Blocker et al, 1999; De Geyter et al, 2000). Dickenson et al showed that besides forming large channels, purified IpaB could assemble into tetramers, and form small pore-like structures that presumably serve as scaffold for translocon insertion into membrane (Dickenson et al, 2013) Together, these works highlight distinct functions of IpaB, either serving as a structural translocator component for bacterial effector delivery into host cells or as a potent effector to induce endolysosomal leakage and promote macrophages pyroptosis. The preliminary results concerning Listeria require further investigations in a more physiological model, but it is tempting to speculate that the findings on Rab involvement in Shigella vacuolar rupture may be extended to other cytosolic pathogens
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