title: VraH Is the Third Component of the Staphylococcus aureus VraDEH System Involved in Gallidermin and Daptomycin Resistance and Pathogenicity.
abstract: In bacteria, extracellular signals are transduced into the cell predominantly by two-component systems (TCSs) comprising a regulatory unit triggered by a specific signal. Some of the TCSs control executing units such as ABC transporters involved in antibiotic resistance. For instance, inStaphylococcus aureus, activation of BraSR leads to the upregulation ofvraDEexpression that encodes an ABC transporter playing a role in bacitracin and nisin resistance. In this study, we show that the small staphylococcal transmembrane protein VraH forms, together with VraDE, a three-component system. Although the expression ofvraHin the absence ofvraDEwas sufficient to mediate low-level resistance, only this VraDEH entity conferred high-level resistance against daptomycin and gallidermin. In most staphylococcal genomes,vraHis located immediately downstream ofvraDE, forming an operon, whereas in some species it is localized differently. In an invertebrate infection model, VraDEH significantly enhancedS. aureuspathogenicity. In analogy to the TCS connectors, VraH can be regarded as an ABC connector that modulates the activity of ABC transporters involved in antibiotic resistance.
authors: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Peter
authors: P
authors: Popella
authors: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Sophia
authors: S
authors: Krauss
authors: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Patrick
authors: P
authors: Ebner
authors: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Mulugeta
authors: M
authors: Nega
authors: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany.
authors: Julia
authors: J
authors: Deibert
authors: Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine, University of Tübingen, Tübingen, Germany friedrich.goetz@uni-tuebingen.de.
authors: Friedrich
authors: F
authors: Götz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D001430:Bacteriocins / Q000494:pharmacology; D003001:Cloning, Molecular; D017576:Daptomycin / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D016680:Genome, Bacterial; D007814:Larva / Q000382:microbiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D009036:Moths / Q000382:microbiology; D009876:Operon; D010455:Peptides / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000472:pathogenicity; D016019:Survival Analysis; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001430:Bacteriocins; D008565:Membrane Proteins; D010455:Peptides; D011994:Recombinant Proteins; C057656:gallidermin; D017576:Daptomycin