Actin-based motility of bacterial pathogens: mechanistic diversity and its impact on virulence.

A diverse spectrum of intracellular bacterial pathogens that inhabit the cytosol have evolved the ability to polymerize actin on their surface to power intracellular actin-based motility (ABM). These include species of Listeria, Burkholderia and Rickettsia, as well as Shigella and Mycobacteria Here, we provide an overview of the roles of bacterial ABM in survival and virulence. Moreover, we survey the molecular mechanisms of actin polymerization in host cells and describe how bacterial pathogens mimic or harness the full diversity of these mechanisms for ABM. Finally, we present ABM through a new lens by comparing motility mechanisms between related species of Listeria, Burkholderia, and Rickettsia Through these comparisons, we hope to illuminate how exploitation of different actin polymerization mechanisms influences ABM as well as pathogenicity and virulence in humans and other animals.

Rickettsia Sca2 is a bacterial formin-like mediator of actin-based motility.

Diverse intracellular pathogens subvert the host actin-polymerization machinery to drive movement within and between cells during infection. Rickettsia in the spotted fever group (SFG) are Gram-negative, obligate intracellular bacterial pathogens that undergo actin-based motility and assemble distinctive 'comet tails' that consist of long, unbranched actin filaments. Despite this distinct organization, it was proposed that actin in Rickettsia comet tails is nucleated by the host Arp2/3 complex and the bacterial protein RickA, which assemble branched actin networks. However, a second bacterial gene, sca2, was recently implicated in actin-tail formation by R. rickettsii. Here, we demonstrate that Sca2 is a bacterial actin-assembly factor that functionally mimics eukaryotic formin proteins. Sca2 nucleates unbranched actin filaments, processively associates with growing barbed ends, requires profilin for efficient elongation, and inhibits the activity of capping protein, all properties shared with formins. Sca2 localizes to the Rickettsia surface and is sufficient to promote the assembly of actin filaments in cytoplasmic extract. These results suggest that Sca2 mimics formins to determine the unique organization of actin filaments in Rickettsia tails and drive bacterial motility, independently of host nucleators.