title: Mutations in the S1 subunit of pertussis toxin that affect secretion.
abstract: Pertussis toxin is a member of the AB(5) family of toxins and is composed of five subunits (S1 to S5) present in a 1:1:1:2:1 ratio. Secretion is a complex process. Each subunit has a secretion signal that mediates transport to the periplasm, where processing and assembly occur. Secretion of the assembled 105-kDa toxin past the outer membrane is mediated by the nine proteins encoded in the ptl operon. Previous studies have shown that S1, the catalytically active A subunit of pertussis toxin, is necessary for efficient secretion, suggesting that a domain on S1 may be required for interaction with the secretion apparatus. Previously, recombinant S1 from four different mutants (serine 54 to glycine, serine 55 to glycine, serine 56 to glycine, and arginine 57 to lysine) was shown to retain catalytic activity. We introduced these mutations into Bordetella pertussis and monitored pertussis toxin production and secretion. No pertussis toxin was detected in the serine 54-to-glycine mutant. The other S1 mutants produced periplasmic pertussis toxin, but little pertussis toxin secretion was observed. The arginine 57-to-lysine mutant had the most dramatic secretion defect. It produced wild-type levels of periplasmic pertussis toxin but secreted only 8% as much toxin as the wild-type strain. This phenotype was similar to that observed for strains with mutations in the ptl genes, suggesting that this region may have a role in pertussis toxin secretion.
authors.affiliation: Department of Molecular Genetics, University of Cincinnati, Cincinnati, Ohio 45267-0524, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Craig-Mylius
authors.forename: T H
authors.initials: TH
authors.lastname: Stenson
authors.forename: A A
authors.initials: AA
authors.lastname: Weiss
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D009154:Mutation; D009876:Operon; D037342:Pertussis Toxin; D013329:Structure-Activity Relationship; D010566:Virulence Factors, Bordetella / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity
chemical_list: D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin