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. colistrains. 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.

Extraintestinal Pathogenic Escherichia coli‐Induced Acute Necrotizing Pneumonia in Cats

“…This might contribute to the reduced number of neutrophils observed in the lungs of the diseased cats that were examined. In addition, CNF-1 evokes oedema, necrosis and other inflammatory changes in the affected tissues (Elliott et al, 1998), which is consistent with our findings of marked alveolar oedema and coagulative necrosis of the alveolar wall and the pulmonary vessels. The P-fimbriae, hlyA and cnf-1 are all part of the same PAI's (Breitschwerdt et al, 2005).…”

Putative roles of the CNF2 and CDTIII toxins in experimental infections with necrotoxigenic Escherichia coli type 2 (NTEC2) strains in calves

“…In conclusion, our results strongly suggest a role of the CNF2 toxin in the occurrence of diarrhea in newborn calves, in contrast to CNF1 [13,14] and CDT-III, but neither in the development of bacteremia nor apparently in the survival of the NTEC2 strains in the bloodstream or internal organs.…”

“…In rabbits, inoculation of intestinal ligated loops with both the wild-type CNF1-producing strain and C600 (CNF1+) caused frank mucoid diarrhea and pathologic intestinal findings in the small and large intestine, including necrosis, hyperplasia and inflammation. However, the use of a CNF-defective mutant did not significantly affect the onset, duration or severity of the diarrhea, although associated with a decrease in intestinal inflammation [13].…”

HlyA knock out yields a saferEscherichia coliA0 34/86 variant with unaffected colonization capacity in piglets

“…The E. coli exotoxin a-haemolysin is thought to be an important virulence factor of extraintestinal and diarrhoeaassociated E. coli strains (Welch et al, 1981;Elliott et al, 1998). Data obtained from both in vivo and in vitro infection models demonstrate toxicity of haemolysin to a wide variety of mammalian cells and organs (Gadeberg et al, 1983;Konig et al, 1986;Bhakdi et al, 1990;Grimminger et al, 1991;Russo et al, 2005).…”