title: Two enteropathogenic Escherichia coli type III secreted proteins, EspA and EspB, are virulence factors.
abstract: Enteropathogenic Escherichia coli (EPEC) belongs to a family of related bacterial pathogens, including enterohemorrhagic Escherichia coli (EHEC) O157:H7 and other human and animal diarrheagenic pathogens that form attaching and effacing (A/E) lesions on host epithelial surfaces. Bacterial secreted Esp proteins and a type III secretion system are conserved among these pathogens and trigger host cell signal transduction pathways and cytoskeletal rearrangements, and mediate intimate bacterial adherence to epithelial cell surfaces in vitro. However, their role in pathogenesis is still unclear. To investigate the role of Esp proteins in disease, mutations in espA and espB were constructed in rabbit EPEC serotype O103 and infection characteristics were compared to that of the wild-type strain using histology, scanning and transmission electron microscopy, and confocal laser scanning microscopy in a weaned rabbit infection model. The virulence of EspA and EspB mutant strains was severely attenuated. Additionally, neither mutant strain formed A/E lesions, nor did either one cause cytoskeletal actin rearrangements beneath the attached bacteria in the rabbit intestine. Collectively, this study shows for the first time that the type III secreted proteins EspA and EspB are needed to form A/E lesions in vivo and are indeed virulence factors. It also confirms the role of A/E lesions in disease processes.
authors.affiliation: Biotechnology Laboratory, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
authors.forename: A
authors.initials: A
authors.lastname: Abe
authors.forename: U
authors.initials: U
authors.lastname: Heczko
authors.forename: R G
authors.initials: RG
authors.lastname: Hegele
authors.forename: B
authors.initials: B
authors.lastname: Brett Finlay
mesh_terms: D000199:Actins / Q000032:analysis; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D004927:Escherichia coli Infections / Q000235:genetics* / Q000401:mortality; D019453:Escherichia coli O157 / Q000235:genetics / Q000472:pathogenicity*; D029968:Escherichia coli Proteins; D006367:HeLa Cells; D006651:Histocytochemistry; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines / Q000382:microbiology / Q000473:pathology; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010581:Peyer's Patches / Q000382:microbiology / Q000473:pathology; D010750:Phosphoproteins / Q000032:analysis; D011817:Rabbits; D014774:Virulence / Q000235:genetics
chemical_list: D000199:Actins; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; C087863:EaeB protein, E coli; D029968:Escherichia coli Proteins; C102051:EspA protein, E coli; D010750:Phosphoproteins