BipA: a tyrosine‐phosphorylated GTPase that mediates interactions between enteropathogenic Escherichia coli (EPEC) and epithelial cells

Abstract

SummaryWe report the functional characterization of BipA, a GTPase that undergoes tyrosine phosphorylation in an enteropathogenic Escherichia coli (EPEC) strain. BipA ¹ mutants adhere to cultured epithelial cells but fail to trigger the characteristic cytoskeletal rearrangements found in cells infected with wild-type EPEC. In contrast, increased expression of BipA enhances actin remodelling and results in the hyperformation of pseudopods. BipA appears to be the first example of a new class of virulence regulator, as it also controls flagellamediated cell motility and resistance to the antibacterial effects of a human host defence protein. Its striking sequence similarity to ribosome-binding elongation factors suggests that it uses a novel mechanism to modulate gene expression.

Integration host factor (IHF) mediates repression of flagella in enteropathogenic and enterohaemorrhagic Escherichia coli

“…This phenotype is similar to that of the EPEC bipA mutant previously reported by Farris et al (1998). Therefore, it is conceivable that, like IHF, BipA is also required for expression of the LEE genes and repression of flhDC.…”

Regulation of the Escherichia coli K5 Capsule Gene Cluster: Evidence for the Roles of H-NS, BipA, and Integration Host Factor in Regulation of Group 2 Capsule Gene Clusters in Pathogenic E. coli

“…The BipA protein was identified as a protein that was phosphorylated on a tyrosine residue in enteropathogenic E. coli (EPEC) strains (12,13). In addition, EPEC bipA mutants do not trigger cytoskeletal rearrangements in host cells, are hypersensitive to the host defense protein BPI, and demonstrate increased mobility and flagellum expression (12).…”

“…The BipA protein was identified as a protein that was phosphorylated on a tyrosine residue in enteropathogenic E. coli (EPEC) strains (12,13). In addition, EPEC bipA mutants do not trigger cytoskeletal rearrangements in host cells, are hypersensitive to the host defense protein BPI, and demonstrate increased mobility and flagellum expression (12). The observation that the E. coli BipA protein has GTPase activity and is homologous to both elongation factor G and the TetO resistance protein, both of which interact with the ribosome, leads to the suggestion that the BipA protein may represent a new class of regulators which function via interactions with the ribosome (12).…”

Survey for g‐proteins in the prokaryotic genomes: Prediction of functional roles based on classification

“…66 We have identified LepA members only in eubacterial genomes (Table II) The TypA (Tyrosine phosphorylated protein A)/BipA class is comprised of GTP-binding proteins that get phosphorylated in the cell but the details of their functions are not completely understood. [67][68][69] This class of proteins also shares overall sequence similarity to EF-G. Certain experimental evidence suggests that it interacts with ribosome in a GTP-dependent manner and shows a novel mechanism of regulation of the expression of the target protein. (Table II) and the archaebacterial genomes.…”