RRC ID 35544
Author Morita-Ishihara T, Miura M, Iyoda S, Izumiya H, Watanabe H, Ohnishi M, Terajima J.
Title EspO1-2 regulates EspM2-mediated RhoA activity to stabilize formation of focal adhesions in enterohemorrhagic Escherichia coli-infected host cells.
Journal PLoS ONE
Abstract Enterohemorrhagic Escherichia coli (EHEC) Sakai strain encodes two homologous type III effectors, EspO1-1 and EspO1-2. These EspO1s have amino acid sequence homology with Shigella OspE, which targets integrin-linked kinase to stabilize formation of focal adhesions (FAs). Like OspE, EspO1-1 was localized to FAs in EHEC-infected cells, but EspO1-2 was localized in the cytoplasm. An EHEC ΔespO1-1ΔespO1-2 double mutant induced cell rounding and FA loss in most of infected cells, but neither the ΔespO1-1 nor ΔespO1-2 single mutant did. These results suggested that EspO1-2 functioned in the cytoplasm by a different mechanism from EspO1-1 and OspE. Since several type III effectors modulate Rho GTPase, which contributes to FA formation, we investigated whether EspO1-2 modulates the function of these type III effectors. We identified a direct interaction between EspO1-2 and EspM2, which acts as a RhoA guanine nucleotide exchange factor. Upon ectopic co-expression, EspO1-2 co-localized with EspM2 in the cytoplasm and suppressed EspM2-mediated stress fiber formation. Consistent with these findings, an ΔespO1-1ΔespO1-2ΔespM2 triple mutant did not induce cell rounding in epithelial cells. These results indicated that EspO1-2 interacted with EspM2 to regulate EspM2-mediated RhoA activity and stabilize FA formation during EHEC infection.
Volume 8(2)
Pages e55960
Published 2013
DOI 10.1371/journal.pone.0055960
PII PONE-D-12-20164
PMID 23409096
PMC PMC3568036
MeSH Actins / metabolism Amino Acid Sequence Cell Line Cell Shape Cytoplasm / metabolism Enterohemorrhagic Escherichia coli / physiology* Escherichia coli Proteins / chemistry Escherichia coli Proteins / genetics Escherichia coli Proteins / metabolism* Focal Adhesions / metabolism* Host-Pathogen Interactions Humans Microfilament Proteins / chemistry Microfilament Proteins / genetics Microfilament Proteins / metabolism* Models, Biological Molecular Sequence Data Protein Binding Protein Stability Protein Transport Sequence Alignment Signal Transduction Stress Fibers / metabolism rhoA GTP-Binding Protein / metabolism*
IF 2.776
Times Cited 4
Prokaryotes E. coli pTH18cr pK19