Structural and Functional Studies of Virulence Factor Homologs EspG and VirA

Abstract

Virulence effectors are a diverse group of proteins secreted by pathogenic bacteria to enable infection by concertedly acting to obstruct host defenses. A major step during invasion and spread for intracellular pathogens and during attachment for adherent pathogens is to alter the host cell cytoskeleton. A combination of structural and functional studies was used to probe the roles of two effectors in cytoskeleton rearrangement during pathogenesis of E. coli and Shigella. Structural studies indicate that EspG from E. coli and VirA from Shigella are structurally similar proteins, yet functional studies indicate that they have different cellular targets. EspG can functionally substitute for VirA, suggesting that these effectors target the same cellular pathway and likely bind similar ligands. Our data indicate that both effectors promote actin reorganization rather than catalyze microtubule destruction as originally proposed.