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Mol Microbiol. 2016 Dec;102(5):850-864. doi: 10.1111/mmi.13495. Epub 2016 Sep 27.

The role of two branched-chain amino acid transporters in Staphylococcus aureus growth, membrane fatty acid composition and virulence.

Author information

1
Department of Microbiology and Immunology, University of Western Ontario, London, ON, Canada.
2
School of Biological Sciences, Illinois State University, Normal, IL, USA.

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.

PMID:
27589208
PMCID:
PMC6225994
DOI:
10.1111/mmi.13495
[Indexed for MEDLINE]
Free PMC Article

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