title: Novel cholix toxin variants, ADP-ribosylating toxins in Vibrio cholerae non-O1/non-O139 strains, and their pathogenicity.
abstract: Cholix toxin (ChxA) is a recently discovered exotoxin in Vibrio cholerae which has been characterized as a third member of the eukaryotic elongation factor 2-specific ADP-ribosyltransferase toxins, in addition to exotoxin A of Pseudomonas aeruginosa and diphtheria toxin of Corynebacterium diphtheriae. These toxins consist of three characteristic domains for receptor binding, translocation, and catalysis. However, there is little information about the prevalence of chxA and its genetic variations and pathogenic mechanisms. In this study, we screened the chxA gene in a large number (n = 765) of V. cholerae strains and observed its presence exclusively in non-O1/non-O139 strains (27.0%; 53 of 196) and not in O1 (n = 485) or O139 (n = 84). Sequencing of these 53 chxA genes generated 29 subtypes which were grouped into three clusters designated chxA I, chxA II, and chxA III. chxA I belongs to the prototype, while chxA II and chxA III are newly discovered variants. ChxA II and ChxA III had unique receptor binding and catalytic domains, respectively, in comparison to ChxA I. Recombinant ChxA I (rChxA I) and rChxA II but not rChxA III showed variable cytotoxic effects on different eukaryotic cells. Although rChxA II was more lethal to mice than rChxA I when injected intravenously, no enterotoxicity of any rChxA was observed in a rabbit ileal loop test. Hepatocytes showed coagulation necrosis in rChxA I- or rChxA II-treated mice, seemingly the major target for ChxA. The present study illustrates the potential of ChxA as an important virulence factor in non-O1/non-O139 V. cholerae, which may be associated with extraintestinal infections rather than enterotoxicity.
authors.affiliation: International Prevention of Epidemics, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan.
authors.forename: Sharda Prasad
authors.initials: SP
authors.lastname: Awasthi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Asakura
authors.forename: Nityananda
authors.initials: N
authors.lastname: Chowdhury
authors.forename: Sucharit Basu
authors.initials: SB
authors.lastname: Neogi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Hinenoya
authors.forename: Hossain M
authors.initials: HM
authors.lastname: Golbar
authors.forename: Jyoji
authors.initials: J
authors.lastname: Yamate
authors.forename: Eiji
authors.initials: E
authors.lastname: Arakawa
authors.forename: Toshiji
authors.initials: T
authors.lastname: Tada
authors.forename: T
authors.initials: T
authors.lastname: Ramamurthy
authors.forename: Shinji
authors.initials: S
authors.lastname: Yamasaki
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics*; D020727:ADP-Ribosylation Factors / Q000235:genetics*; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics; D001427:Bacterial Toxins / Q000235:genetics*; D002772:Cholera Toxin / Q000235:genetics*; D014644:Genetic Variation; D022781:Hepatocytes / Q000382:microbiology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D011817:Rabbits; D014734:Vibrio cholerae / Q000235:genetics* / Q000472:pathogenicity; D041242:Vibrio cholerae O139 / Q000201:enzymology / Q000235:genetics* / Q000472:pathogenicity; D044163:Vibrio cholerae non-O1 / Q000235:genetics* / Q000472:pathogenicity; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D037521:Virulence Factors; D002772:Cholera Toxin; D036002:ADP Ribose Transferases; D020727:ADP-Ribosylation Factors; C529269:cholix toxin, Vibrio cholerae