Striking a balance: Modulation of the actin cytoskeleton by Salmonella

Salmonella spp. have evolved the ability to enter into cells that are norma lly nonphagocytic. The internalization process is the result of a remarkabl e interaction between the bacteria and the host cells. Immediately on conta ct, Salmonella delivers a number of bacterial effector proteins into the ho st cell cytosol through the function of a specialized organelle termed the type III secretion system. Initially, two of the delivered proteins, SopE a nd SopB, stimulate the small GTP-binding proteins Cdc42 and Rac. SopE is an exchange factor for these GTPases, and SopB is an inositol polyphosphate p hosphatase. Stimulation of Cdc42 and Rac leads to marked actin cytoskeleton rearrangements, which are further enhanced by SipA, a Salmonella protein a lso delivered into the host cell by the type III secretion system, SipA low ers the critical concentration of C-actin, stabilizes F-actin at the site o f bacterial entry, and increases the bundling activity of the host-cell pro tein T-plastin (fimbrin). The cellular responses stimulated by Salmonella a re short-lived; therefore, immediately after bacterial entry, the cell rega ins 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 effecters SopE and So pB. The balanced interaction of Salmonella with host cells constitutes a re markable example of the sophisticated nature of a pathogen/host relationshi p shaped by evolution through a longstanding coexistence.