title: Peptide methionine sulfoxide reductase (MsrA) is not a major virulence determinant for the oral pathogen Actinobacillus actinomycetemcomitans.
abstract: Actinobacillus actinomycetemcomitans is an oral pathogen that is a causative agent for periodontal disease as well as other non-oral infections. The chronic inflammation associated with periodontal diseases suggests that the bacterium must be able to neutralize oxygen intermediates to survive in the host tissues. Methionine sulfoxide reductase (MsrA) is an enzyme that has been demonstrated to have a role in protection against oxidative damage and has also been identified to be required for the proper expression or maintenance of functional adhesins on the surface of several pathogenic bacteria. The A. actinomycetemcomitans homologue of msrA has been isolated and a chromosomal insertion mutant constructed by allele replacement mutagenesis. Inactivation of the gene led to a complete loss of enzymic activity toward a synthetic substrate. However, the isogenic mutant was not more sensitive to oxidative stress or less adherent to epithelial cells as compared with the parent strain. These data suggest that this strain of A. actinomycetemcomitans has redundant systems that compensate for the MsrA activities ascribed for other organisms.
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA1.
authors.forename: Keith P
authors.initials: KP
authors.lastname: Mintz
authors.affiliation: Laboratory of Biochemistry, NHLBI, National Institutes of Health, Bethesda, MD, USA2.
authors.forename: Jackob
authors.initials: J
authors.lastname: Moskovitz
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA1.
authors.forename: Hui
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA1.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Fives-Taylor
mesh_terms: D016976:Aggregatibacter actinomycetemcomitans / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D026901:Membrane Transport Proteins; D051150:Methionine Sulfoxide Reductases; D008969:Molecular Sequence Data; D009055:Mouth / Q000382:microbiology*; D018384:Oxidative Stress / Q000502:physiology; D010088:Oxidoreductases / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D010510:Periodontal Diseases / Q000382:microbiology; D017386:Sequence Homology, Amino Acid; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C066202:msrA protein, Staphylococcus epidermidis; D010088:Oxidoreductases; D051150:Methionine Sulfoxide Reductases; C027219:methionine sulfoxide reductase