title: The role of two branched-chain amino acid transporters in Staphylococcus aureus growth, membrane fatty acid composition and virulence.
abstract: The branched-chain amino acids (BCAAs) are vital to both growth and virulence of the human pathogen Staphylococcus aureus. In addition to supporting protein synthesis, the BCAAs serve as precursors for branched-chain fatty acids (BCFAs), which are predominant membrane fatty acids, and, in association with the global regulatory protein CodY, the BCAAs are key co-regulators of virulence factors. Despite these critical functions, S. aureus represses Leu and Val synthesis, instead preferring to acquire them from the extracellular milieu. We previously identified BrnQ1 as a BCAA transporter, yet a brnQ1 mutant remained capable of BCAA acquisition. Here, we describe BcaP as an additional BCAA transporter, and determine that it plays a secondary role to BrnQ1 during S. aureus growth in a chemically defined medium. Furthermore, membrane fatty acid composition analysis revealed that BrnQ1, and not BcaP, is required for transporting Leu and Val to be used for iso-BCFA synthesis. Despite a predominant role for BrnQ1 in vitro, both BrnQ1 and BcaP are required for S. aureus fitness in vivo in a hematogenous spread infection model and a nasal colonisation model. These data demonstrate the importance of BrnQ1 and BcaP for growth, environmental adaptation and virulence of S. aureus.
authors: Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada.
authors: Julienne C
authors: JC
authors: Kaiser
authors: School of Biological Sciences, Illinois State University, Normal, IL, USA.
authors: Suranjana
authors: S
authors: Sen
authors: Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada.
authors: Anshul
authors: A
authors: Sinha
authors: School of Biological Sciences, Illinois State University, Normal, IL, USA.
authors: Brian J
authors: BJ
authors: Wilkinson
authors: Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada.
authors: David E
authors: DE
authors: Heinrichs
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism; D001692:Biological Transport; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D026901:Membrane Transport Proteins / Q000378:metabolism; D013203:Staphylococcal Infections / Q000382:microbiology; D013211:Staphylococcus aureus / Q000254:growth & development* / Q000378:metabolism* / Q000472:pathogenicity; D014157:Transcription Factors / Q000378:metabolism; D014774:Virulence / Q000502:physiology
chemical_list: D000597:Amino Acids, Branched-Chain; D001426:Bacterial Proteins; D005227:Fatty Acids; D026901:Membrane Transport Proteins; D014157:Transcription Factors