title: Amino-terminal domain of the El Tor haemolysin of Vibrio cholerae O1 is expressed in classical strains and is cytotoxic.
abstract: Previous studies have shown that the classical isolates of Vibrio cholerae possess an 11 bp deletion in the structural gene for the El Tor haemolysin leading to the production of a 27 kDa non-haemolytic truncated product HlyA* compared to the 82 kDa haemolysin, HlyA. These studies were designed to assess whether this truncated product had any biological activity. A KmR cartridge was introduced into the hlyA gene effectively eliminating the haemolysin. This was recombined into the chromosome of a variety of strains and isogenic pairs were examined in a number of systems. These studies suggest that the haemolytic (cytolytic) domain of HlyA resides at the C-terminus and that the N-terminus, which is conserved as HlyA* in classical strains, possesses enterotoxic (cytotoxic) activity. Experiments with the cholera-toxinless vaccine candidate JBK70 and its hlyA::KmR mutant suggest that HlyA* may be responsible for the residual diarrhoea observed in cholera-toxinless vaccine strains.
authors.affiliation: Department of Microbiology and Immunology, University of Adelaide, SA.
authors.forename: R A
authors.initials: RA
authors.lastname: Alm
authors.forename: G
authors.initials: G
authors.lastname: Mayrhofer
authors.forename: I
authors.initials: I
authors.lastname: Kotlarski
authors.forename: P A
authors.initials: PA
authors.lastname: Manning
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000633:toxicity*; D001834:Body Water / Q000378:metabolism; D002470:Cell Survival; D004591:Electrophoresis, Polyacrylamide Gel; D029968:Escherichia coli Proteins; D015870:Gene Expression; D006460:Hemolysin Proteins; D006801:Humans; D007082:Ileum / Q000378:metabolism; D051379:Mice; D009154:Mutation; D009693:Nucleic Acid Hybridization; D010957:Plasmids / Q000235:genetics; D014407:Tumor Cells, Cultured; D014734:Vibrio cholerae / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006460:Hemolysin Proteins; C036507:Hlya protein, E coli