title: The chromosomal nature of LT-II enterotoxins solved: a lambdoid prophage encodes both LT-II and one of two novel pertussis-toxin-like toxin family members in type II enterotoxigenic Escherichia coli.
abstract: Heat-labile enterotoxins (LT) of enterotoxigenic Escherichia coli (ETEC) are structurally and functionally related to cholera toxin (CT). LT-I toxins are plasmid-encoded and flanked by IS elements, while LT-II toxins of type II ETEC are chromosomally encoded with flanking genes that appear phage related. Here, I determined the complete genomic sequence of the locus for the LT-IIa type strain SA53, and show that the LT-IIa genes are encoded by a 51 239 bp lambdoid prophage integrated at the rac locus, the site of a defective prophage in E. coli K12 strains. Of 50 LT-IIa and LT-IIc, 46 prophages also encode one member of two novel two-gene ADP-ribosyltransferase toxin families that are both related to pertussis toxin, which I named eplBA or ealAB, respectively. The eplBA and ealAB genes are syntenic with the Shiga toxin loci in their lambdoid prophages of the enteric pathogen enterohemorrhagic E. coli. These novel AB(5) toxins show pertussis-toxin-like activity on tissue culture cells, and like pertussis toxin bind to sialic acid containing glycoprotein ligands. Type II ETEC are the first mucosal pathogens known to simultaneously produce two ADP-ribosylating toxins predicted to act on and modulate activity of both stimulatory and inhibitory alpha subunits of host cell heterotrimeric G-proteins.
authors.affiliation: Department of Immunology and Microbiology, University of Colorado School of Medicine, 12800 E 19th Ave, Aurora CO 80045, USA michael.jobling@ucdenver.edu.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Jobling
mesh_terms: D036002:ADP Ribose Transferases / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D001427:Bacterial Toxins / Q000235:genetics*; D001483:Base Sequence; D016466:CHO Cells; D002460:Cell Line; D003412:Cricetulus; D054307:Enterotoxigenic Escherichia coli / Q000235:genetics* / Q000472:pathogenicity*; D004768:Enterotoxins / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D037342:Pertussis Toxin / Q000235:genetics*; D039002:Prophages / Q000235:genetics*; D017422:Sequence Analysis, DNA
chemical_list: D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; C027538:heat-labile enterotoxin, E coli; D036002:ADP Ribose Transferases; D037342:Pertussis Toxin
keywords: ADP-ribosyltransferase; ETEC; heat-labile enterotoxin; pertussis-toxin-like toxin; prophage