Striking a balance: Modulation of the actin cytoskeleton bySalmonella

Abstract

Salmonella spp. have evolved the ability to enter into cells that are normally nonphagocytic. The internalization process is the result of a remarkable interaction between the bacteria and the host cells. Immediately on contact, Salmonella delivers a number of bacterial effector proteins into the host cell cytosol through the function of a specialized organelle termed the type III secretion system. Initially, two of the delivered proteins, SopE and SopB, stimulate the small GTP-binding proteins Cdc42 and Rac. SopE is an exchange factor for these GTPases, and SopB is an inositol polyphosphate phosphatase. Stimulation of Cdc42 and Rac leads to marked actin cytoskeleton rearrangements, which are further enhanced by SipA, a Salmonella protein also delivered into the host cell by the type III secretion system. SipA lowers the critical concentration of G-actin, stabilizes F-actin at the site of bacterial entry, and increases the bundling activity of the host-cell protein T-plastin (fimbrin). The cellular responses stimulated by Salmonella are short-lived; therefore, immediately after bacterial entry, the cell regains its normal architecture. Remarkably, this process is mediated by SptP, another target of the type III secretion system. SptP exert its function by serving as a GTPase-activating protein for Cdc42 and Rac, turning these G proteins off after their stimulation by the bacterial effectors SopE and SopB. The balanced interaction of Salmonella with host cells constitutes a remarkable example of the sophisticated nature of a pathogen͞host relationship shaped by evolution through a longstanding coexistence.

Quantitative proteomics of intracellular Porphyromonas gingivalis

“…Organisms that colonize human mucosal surface have engaged in a long standing evolutionary association with the host and many, including opportunistic pathogens such as P. gingivalis, have become host adapted [62]. Indeed, the ability of P. gingivalis to survive within gingival epithelial cells, without causing excessive harm to the host, indicates an extensive degree of adaptation.…”

A new release on life: emerging concepts in proteolysis and parasite invasion

“…A number of mechanisms are used which differ considerably in their detail, but a common feature is the exploitation of host cell signalling pathways to induce localized rearrangements in host cell actin organization. The bacteria are then internalized by a process somewhat analogous to phagocytosis (Finlay and Cossart, 1997;Galan and Zhou, 2000), ending up within a membrane-bound vacuole. Subsequent bacterial replication takes place within the vacuole (which is often modified by the invader so as to prevent fusion with lysosomes), or within the host cell cytosol after rupture of the vacuole.…”

The C Terminus of SipC Binds and Bundles F-actin to Promote Salmonella Invasion

“…These diseases are among the most common food-borne diseases in humans and represent a major public health and economical burden worldwide (1)(2)(3)(4)(5)(6). Salmonella species have evolved sophisticated virulence mechanisms to manipulate host cell functions to their own benefit.…”