title: Functional characterization of TcaA: minimal requirement for teicoplanin susceptibility and role in Caenorhabditis elegans virulence.
abstract: The inactivation of TcaA contributes to intrinsic teicoplanin resistance in experimental and clinical isolates of glycopeptide-intermediate resistant Staphylococcus aureus. PhoA fusions confirmed that TcaA is a transmembrane protein with a short intracellular N-terminal domain containing a C-4 zinc finger binding motif, a single membrane-spanning domain, and a large extracellular C-terminal domain. The region conferring teicoplanin susceptibility was narrowed down to the transmembrane part and the first third of the extracellular domain of TcaA, suggesting that neither the C-4 zinc finger binding motif nor the C terminus contributed to teicoplanin susceptibility. TcaA belongs to the cell wall stress stimulon, which comprises a set of genes universally upregulated by cell wall damage. Induction of tcaA was shown to be fully dependent on the two-component regulatory system VraSR. A 66-bp region upstream of the transcriptional start site, which contained an inverted repeat partially covering the promoter box, was shown to be essential for VraSR-mediated induction by cell wall stress. Interestingly, the induction or overexpression of tcaA did not contribute further to teicoplanin susceptibility, suggesting that small amounts of TcaA, such as those present under normal uninduced conditions, were sufficient for TcaA-mediated teicoplanin susceptibility. The strong attenuation of tcaA deletion mutants in a Caenorhabditis elegans survival assay suggested that TcaA may, in addition to affecting glycopeptide susceptibility, also play a role in virulence.
authors: Institute of Medical Microbiology, University of Zurich, Gloriastr. 32, 8006 Zurich, Switzerland. mccallum@immv.uzh.ch
authors: Nadine
authors: N
authors: McCallum
authors: Ann Karen C
authors: AK
authors: Brassinga
authors: Costi D
authors: CD
authors: Sifri
authors: Brigitte
authors: B
authors: Berger-Bächi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000382:microbiology*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D005816:Genetic Complementation Test; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic / Q000235:genetics; D013211:Staphylococcus aureus / Q000235:genetics* / Q000472:pathogenicity; D016019:Survival Analysis; D017334:Teicoplanin / Q000494:pharmacology*; D014774:Virulence / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; D017334:Teicoplanin
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