Inhibition of WAVE Regulatory Complex Activation by a Bacterial Virulence Effector Counteracts Pathogen Phagocytosis.

ABSTRACT: To establish pathogenicity, bacteria must evade phagocytosis directed by remodeling of the actin cytoskeleton. We show that macrophages facilitate pathogen phagocytosis through actin polymerization mediated by the WAVE regulatory complex (WRC), small GTPases Arf and Rac1, and the Arf1 activator ARNO. To establish extracellular infections, enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) Escherichia coli hijack the actin cytoskeleton by injecting virulence effectors into the host cell. Here, we find that the virulence effector EspG counteracts WRC-dependent phagocytosis, enabling EPEC and EHEC to remain extracellular. By reconstituting membrane-associated actin polymerization, we find that EspG disabled WRC activation through two mechanisms: EspG interaction with Arf6 blocked signaling

SUBMITTER: Humphreys D 

PROVIDER: S-EPMC5081413 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature