Mobilization of the actin cytoskeleton by microbial pathogens

Abstract

Diverse bacterial pathogens hijack the actin cytoskeleton of host cells to facilitate attachment, internalization, or spread. Our focus is on the human pathogen Rickettsia parkeri, which undergoes actin‐based motility in the cell cytosol to promote cell‐to‐cell spread during infection. R. parkeri and other Rickettsiae are unusual in expressing two bacterial proteins that activate actin polymerization: RickA activates the host actin‐nucleating Arp2/3 complex while Sca2 directly nucleates actin by mimicking host formins. By following Rickettsia throughout infection, we discovered two temporally and mechanistically distinct phases of motility. Early motility is slow, paths of movement are curved, and actin polymerization requires the host Arp2/3 complex. In contrast, late motility is rapid, paths of movement are straighter, and actin polymerization is independent of the Arp2/3 complex. Rickettsia with a transposon insertion in RickA are defective only in early motility, whereas bacteria with a transposon insertion in Sca2 fail to undergo late motility. Thus, RickA activates the Arp2/3 complex during early actin‐based motility, while Sca2 independently nucleates actin during late motility. Rickettsia are unusual in their ability to promote two temporally and mechanistically distinct phases of motility during infection, and each phase may perform a unique function in the bacterial life cycle.