title: Characterization of the roles of hemolysin and other toxins in enteropathy caused by alpha-hemolytic Escherichia coli linked to human diarrhea.
abstract: Escherichia coli strains producing alpha-hemolysin have been associated with diarrhea in several studies, but it has not been clearly demonstrated that these strains are enteropathogens or that alpha-hemolysin is an enteric virulence factor. Such strains are generally regarded as avirulent commensals. We examined a collection of diarrhea-associated hemolytic E. coli (DHEC) strains for virulence factors. No strain produced classic enterotoxins, but they all produced an alpha-hemolysin that was indistinguishable from that of uropathogenic E. coli strains. DHEC strains also produced other toxins including cytotoxic necrotizing factor 1 (CNF1) and novel toxins, including a cell-detaching cytotoxin and a toxin that causes HeLa cell elongation. DHEC strains were enteropathogenic in the RITARD (reversible intestinal tie adult rabbit diarrhea) model of diarrhea, causing characteristic enteropathies, including inflammation, necrosis, and colonic cell hyperplasia in both small and large intestines. Alpha-hemolysin appeared to be a major virulence factor in this model since it conferred virulence to nonpathogenic E. coli strains. Other virulence factors also appear to be contributing to virulence. These findings support the epidemiologic link to diarrhea and suggest that further research into the role of DHEC and alpha-hemolysin in enteric disease is warranted.
authors.affiliation: Center for Vaccine Development, University of Maryland School of Medicine, Baltimore 21201, USA. selliot@umaryland.edu
authors.forename: S J
authors.initials: SJ
authors.lastname: Elliott
authors.forename: S
authors.initials: S
authors.lastname: Srinivas
authors.forename: M J
authors.initials: MJ
authors.lastname: Albert
authors.forename: K
authors.initials: K
authors.lastname: Alam
authors.forename: R M
authors.initials: RM
authors.lastname: Robins-Browne
authors.forename: S T
authors.initials: ST
authors.lastname: Gunzburg
authors.forename: B J
authors.initials: BJ
authors.lastname: Mee
authors.forename: B J
authors.initials: BJ
authors.lastname: Chang
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000633:toxicity*; D001427:Bacterial Toxins / Q000235:genetics / Q000633:toxicity*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D003603:Cytotoxins / Q000235:genetics / Q000633:toxicity; D003967:Diarrhea / Q000209:etiology*; D004926:Escherichia coli / Q000472:pathogenicity*; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins / Q000633:toxicity*; D006801:Humans; D011817:Rabbits
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D003603:Cytotoxins; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; C036507:Hlya protein, E coli; C060296:cytotoxic necrotizing factor type 1