title: The bacA gene, which determines bacitracin susceptibility in Streptococcus pneumoniae and Staphylococcus aureus, is also required for virulence.
abstract: Homologues of Escherichia coli bacA, encoding extremely hydrophobic proteins, were identified in the genomes of Staphylococcus aureus and Streptococcus pneumoniae. Allelic replacement mutagenesis demonstrated that the gene is not essential for in vitro growth in either organism, and the mutants showed no significant changes in growth rate or morphology. The Staph. aureus bacA mutant showed slightly reduced virulence in a mouse model of infection and an eightfold increase in bacitracin susceptibility. However, a Strep. pneumoniae bacA mutant was highly attenuated in a mouse model of infection, and demonstrated an increase in susceptibility to bacitracin of up to 160000-fold. These observations are consistent with the previously proposed role of BacA protein as undecaprenol kinase.
authors.affiliation: Anti-Infective Research (UP1345), SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA19426-0989, USA1.
authors.forename: Alison F
authors.initials: AF
authors.lastname: Chalker
authors.affiliation: Anti-Infective Research (UP1345), SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA19426-0989, USA1.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Ingraham
authors.affiliation: Anti-Infective Research (UP1345), SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA19426-0989, USA1.
authors.forename: R Dwayne
authors.initials: RD
authors.lastname: Lunsford
authors.affiliation: Anti-Infective Research (UP1345), SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA19426-0989, USA1.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Bryant
authors.affiliation: Anti-Infective Research (UP1345), SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA19426-0989, USA1.
authors.forename: Joanna
authors.initials: J
authors.lastname: Bryant
authors.affiliation: Anti-Infective Research (UP1345), SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA19426-0989, USA1.
authors.forename: Nicola G
authors.initials: NG
authors.lastname: Wallis
authors.affiliation: Anti-Infective Research (UP1345), SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA19426-0989, USA1.
authors.forename: John P
authors.initials: JP
authors.lastname: Broskey
authors.affiliation: Anti-Infective Research (UP1345), SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA19426-0989, USA1.
authors.forename: Stewart C
authors.initials: SC
authors.lastname: Pearson
authors.affiliation: Anti-Infective Research (UP1345), SmithKline Beecham Pharmaceuticals, 1250 South Collegeville Road, PO Box 5089, Collegeville, PA19426-0989, USA1.
authors.forename: David J
authors.initials: DJ
authors.lastname: Holmes
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001414:Bacitracin / Q000494:pharmacology; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D026901:Membrane Transport Proteins; D051379:Mice; D008808:Mice, Inbred CBA; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000502:physiology; D011008:Pneumococcal Infections / Q000382:microbiology; D017386:Sequence Homology, Amino Acid; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C082397:bacA protein, Rhizobium meliloti; D001414:Bacitracin; D017853:Phosphotransferases (Alcohol Group Acceptor); C021454:undecaprenol kinase