The glutathione import system satisfies the Staphylococcus aureus nutrient sulfur requirement and promotes interspecies competition.

Autor: Lensmire JM; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America., Wischer MR; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America., Kraemer-Zimpel C; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America., Kies PJ; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America., Sosinski L; Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, Michigan, United States of America., Ensink E; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, United States of America., Dodson JP; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America., Shook JC; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America., Delekta PC; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America., Cooper CC; Department of Medicine, Division of Infectious Disease, Michigan State University, East Lansing, Michigan, United States of America., Havlichek DH Jr; Department of Medicine, Division of Infectious Disease, Michigan State University, East Lansing, Michigan, United States of America., Mulks MH; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America., Lunt SY; Department of Biochemistry and Molecular Biology, Michigan State University, East Lansing, Michigan, United States of America.; Department of Chemical Engineering and Materials Science, Michigan State University, East Lansing, Michigan, United States of America., Ravi J; Department of Biomedical Informatics, Center for Health Artificial Intelligence, University of Colorado Anschutz, Aurora, Colorado, United States of America., Hammer ND; Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing, Michigan, United States of America.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2023 Jul 07; Vol. 19 (7), pp. e1010834. Date of Electronic Publication: 2023 Jul 07 (Print Publication: 2023).
DOI: 10.1371/journal.pgen.1010834
Abstrakt: Sulfur is an indispensable element for bacterial proliferation. Prior studies demonstrated that the human pathogen Staphylococcus aureus utilizes glutathione (GSH) as a source of nutrient sulfur; however, mechanisms of GSH acquisition are not defined. Here, we identify a five-gene locus comprising a putative ABC-transporter and predicted γ-glutamyl transpeptidase (ggt) that promotes S. aureus proliferation in medium supplemented with either reduced or oxidized GSH (GSSG) as the sole source of nutrient sulfur. Based on these phenotypes, we name this transporter operon the glutathione import system (gisABCD). Ggt is encoded within the gisBCD operon, and we show that the enzyme is capable of liberating glutamate using either GSH or GSSG as substrates, demonstrating it is a bona fide γ-glutamyl transpeptidase. We also determine that Ggt is expressed in the cytoplasm, representing only the second example of cytoplasmic Ggt localization, the other being Neisseria meningitidis. Bioinformatic analyses revealed that Staphylococcus species closely related to S. aureus encode GisABCD-Ggt homologs. However, homologous systems were not detected in Staphylococcus epidermidis. Consequently, we establish that GisABCD-Ggt provides a competitive advantage for S. aureus over S. epidermidis in a GSH- and GSSG-dependent manner. Overall, this study describes the discovery of a nutrient sulfur acquisition system in S. aureus that targets GSSG in addition to GSH and promotes competition against other staphylococci commonly associated with the human microbiota.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2023 Lensmire et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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