title: The role of a stress-response protein in Salmonella typhimurium virulence.
abstract: We recently described the use of selective transposon mutagenesis to generate a series of avirulent mutants of a pathogenic strain of Salmonella typhimurium. Cloning and sequencing of the insertion sites from two of these mutants reveals that both have identical locations within an open reading frame that is highly homologous to a gene, htrA, encoding a heat-shock protein in Escherichia coli. DNA sequence analysis of S. typhimurium htrA reveals the presence of a gene capable of encoding a protein with a calculated Mr of 49316 that has 88.7% protein:protein homology with its E. coli counterpart. In E. coli, lesions in this gene, also known as degP, reduce proteolytic degradation of aberrant periplasmic proteins. Characteristics of the S. typhimurium htrA mutants, 046 and 014, in vivo and in vitro suggested that they are avirulent because of impaired ability to survive and/or replicate in host tissues. In vitro, the S. typhimurium htrA mutants 046 and 014 are not temperature-sensitive but were found to be more susceptible to oxidative stress than the parent, suggesting that they may be less able to withstand oxidative killing within macrophages.
authors.affiliation: Department of Pathology, University of Cambridge, UK.
authors.forename: K
authors.initials: K
authors.lastname: Johnson
authors.forename: I
authors.initials: I
authors.lastname: Charles
authors.forename: G
authors.initials: G
authors.lastname: Dougan
authors.forename: D
authors.initials: D
authors.lastname: Pickard
authors.forename: P
authors.initials: P
authors.lastname: O'Gaora
authors.forename: G
authors.initials: G
authors.lastname: Costa
authors.forename: T
authors.initials: T
authors.lastname: Ali
authors.forename: I
authors.initials: I
authors.lastname: Miller
authors.forename: C
authors.initials: C
authors.lastname: Hormaeche
mesh_terms: D000469:Alkaline Phosphatase / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D003001:Cloning, Molecular; D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D016366:Open Reading Frames; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D012689:Sequence Homology, Nucleic Acid; D014774:Virulence / Q000235:genetics
chemical_list: D004251:DNA Transposable Elements; D004269:DNA, Bacterial; D006360:Heat-Shock Proteins; D000469:Alkaline Phosphatase