The Staphylococcus aureus Cystine Transporters TcyABC and TcyP Facilitate Nutrient Sulfur Acquisition during Infection.

Autor:	Lensmire JM; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA., Dodson JP; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA., Hsueh BY; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA., Wischer MR; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA., Delekta PC; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA., Shook JC; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA., Ottosen EN; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA., Kies PJ; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA., Ravi J; Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan, USA., Hammer ND; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, USA hammern2@msu.edu.
Jazyk:	angličtina
Zdroj:	Infection and immunity [Infect Immun] 2020 Feb 20; Vol. 88 (3). Date of Electronic Publication: 2020 Feb 20 (Print Publication: 2020).
DOI:	10.1128/IAI.00690-19
Abstrakt:	Staphylococcus aureus is a significant human pathogen due to its capacity to cause a multitude of diseases. As such, S. aureus efficiently pillages vital nutrients from the host; however, the molecular mechanisms that support sulfur acquisition during infection have not been established. One of the most abundant extracellular sulfur-containing metabolites within the host is cysteine, which acts as the major redox buffer in the blood by transitioning between reduced and oxidized (cystine) forms. We therefore hypothesized that S. aureus acquires host-derived cysteine and cystine as sources of nutrient sulfur during systemic infection. To test this hypothesis, we used the toxic cystine analogue selenocystine to initially characterize S. aureus homologues of the Bacillus subtilis cystine transporters TcyABC and TcyP. We found that genetic inactivation of both TcyA and TcyP induced selenocystine resistance. The double mutant also failed to proliferate in medium supplemented with cystine, cysteine, or N -acetyl cysteine as the sole sulfur source. However, only TcyABC was necessary for proliferation in defined medium containing homocystine as the sulfur source. Using a murine model of systemic infection, we observed tcyP -dependent competitive defects in the liver and heart, indicating that this sulfur acquisition strategy supports proliferation of S. aureus in these organs. Phylogenetic analyses identified TcyP homologues in many pathogenic species, implying that this sulfur procurement strategy is conserved. In total, this study is the first to experimentally validate sulfur acquisition systems in S. aureus and establish their importance during pathogenesis. (Copyright © 2020 American Society for Microbiology.)
Databáze:	MEDLINE
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