Trends in Microbiology
Volume 9, Issue 12, 1 December 2001, Pages 567-569
Journal home page for Trends in Microbiology

Research update
Collective efforts to modulate the host actin cytoskeleton by Salmonella type III-secreted effector proteins

https://doi.org/10.1016/S0966-842X(01)02227-2Get rights and content

Abstract

The hallmark of Salmonella entry into host cells is extensive rearrangements of the host actin cytoskeleton at the site of Salmonella contact with intestinal epithelial cells. SopE, SopE2 and SopB, three type III effectors of Salmonella pathogenicity island 1 (SPI-1), activate the Cdc42 and Rac1 signal transduction pathways to promote these rearrangements. SipA and SipC, two Salmonella type III-secreted actin-binding proteins, directly modulate host actin dynamics to facilitate bacterial uptake. Salmonella-induced actin cytoskeleton rearrangements are therefore the result of the coordinated action of a group of type III-secreted effector proteins.

Section snippets

Signal interceptors: SopB and SopE command the signal transduction pathways

Salmonella entry into host cells is accompanied by extensive rearrangements of the host cell actin cytoskeleton7, 8. These rearrangements and the subsequent entry of Salmonella are abolished when actin polymerization is inhibited by cytochalasins9. Although many Salmonella genes are required for the induction of such rearrangements, the details of how this reorganization occurs are only now beginning to come to light.

The actin cytoskeleton plays a pivotal role in many cellular processes,

Front-line fighters: SipA and SipC modulate host actin dynamics

The discovery that SipA binds actin was the first indication that Salmonella can modulate host actin dynamics directly and established that, in addition to the effectors that activate the signal transduction pathways involved in actin cytoskeleton rearrangements, Salmonella also dispatches actin-binding proteins into host cells.

In the search for SipA-interacting host proteins, T-plastin (fimbrin) was originally found to form a complex with SipA (Ref. 12); however, no evidence for direct binding

Working together: bacterial and host actin-modulating proteins

One of the most exciting discoveries about actin polymerization is the role of the Arp2/3 complex and its regulation. It illustrates perfectly how signal transduction pathways are tightly coupled with actin-binding proteins to regulate actin dynamics in response to external stimuli. The purified Arp2/3 complex alone can nucleate the formation of actin filaments15. This activity is greatly increased by signaling molecules, such as N-WASP, that mediate the interaction between Cdc42 and the Arp2/3

Challenges ahead

Tremendous progress has been made in understanding the molecular mechanisms of Salmonella-induced actin cytoskeleton rearrangements during the past few years. This exciting field is poised to advance even further as we identify the functions of more type III effectors. It will be extremely interesting to see how they exert their unique functions in a cooperative environment containing not only the effectors themselves but also the vast array of host actin-binding proteins. Furthermore, although

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      Finally, Rac/Cdc42 can interact with additional effectors implicated in actin dynamics and turnover, for instance, p65PAK driving LIM kinase-mediated ADF/cofilin inactivation (Raftopoulou and Hall, 2004). Hence, as observed with other motility processes (Disanza et al., 2005; Loisel et al., 1999), a concerted action of both actin filament nucleators and depolymerizing factors (such as ADF/cofilin) during the different stages of Salmonella entry may be required to allow for efficient invasion (Dai et al., 2004; Zhou, 2001). Together, the exact contributions to Sop-mediated entry of Cdc42 versus Rac activity and of their common as well as distinct downstream actin regulators will require more detailed analyses, certainly including knockout or knockdown approaches in the host.

    • Structure-function analysis of invasion plasmid antigen C (IpaC) from Shigella flexneri

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