Bacterial subversion of host actin dynamics at the plasma membrane

Abstract

Invasion of non-phagocytic cells by a number of bacterial pathogens involves the subversion of the actin cytoskeletal remodelling machinery to produce actin-rich cell surface projections designed to engulf the bacteria. The signalling that occurs to induce these actin-rich structures has considerable overlap among a diverse group of bacteria. The molecular organization within these structures act in concert to internalize the invading pathogen. This dynamic process could be subdivided into three acts - actin recruitment, engulfment, and finally, actin disassembly/internalization. This review will present the current state of knowledge of the molecular processes involved in each stage of bacterial invasion, and provide a perspective that highlights the temporal and spatial control of actin remodelling that occurs during bacterial invasion.

Fig. 1. A schematic diagram of signalling with Listeria and Chlamydia to the actin remodelling machinery

A. Listeria InlB binds to the host cell Met receptor to trigger a signal transduction that activates a variety of signalling molecules that participate in and promote the recruitment and assembly of an F-actin network during invasion. The activation of the Rac GTPase is pivotal to this process. Rac promotes a WAVE2-dependent actin polymerisation and induce LIM kinase activity to inhibit the actin depolymerising activity of cofilin. The localised synthesis of PIP3 and PIP2 ensures the enrichment of adapter/signalling molecules that recognise these phospholipids. B. Actin remodelling during chlamydial invasion depends on two complementary pathways: (i), a signalling mechanism that involves host factors such as the WAVE2 complex; and (ii), a nucleating function of the Type III effector TARP. The signalling component involves the binding of PDGFR molecules at the cell surface to trigger activation of the Rac GTPase. Actin disassembly may involve the effector CT694 and the putative Chlamydia toxin.

Fig. 2. Signalling by EHEC and Salmonella to the actin remodelling machinery

A. The formation of an actin-rich pedestal by EHEC requires the Type III translocation of Tir, which is subsequently embedded in the plasma membrane. There it recruits host signalling proteins, such as IRTKS, which in turn binds the EHEC EspF(U) effector. EspF(U) dimerise and bring N-WASP molecules in close proximity to enhance N-WASP activation. B. Salmonella ruffle formation requires the WAVE2 signalling complex, but recent reports suggest that this is not essential to invasion. Instead, the actin remodelling required for invasion is mediated by the WASH complex. In addition, a parallel pathway consisting of Rho, Rho kinase, and Myosin II cooperates with the WASH pathway to facilitate Salmonella invasion.