{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:26:37Z","timestamp":1790659597806,"version":"4.1.0"},"reference-count":55,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T00:00:00Z","timestamp":1630972800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Reactive oxygen species (ROS) play a crucial role in the cellular defense against\n                    <jats:italic>S. aureus<\/jats:italic>\n                    , as evidenced by the importance of this pathogen in patients lacking the ROS-generating phagocyte NADPH oxidase NOX2. ROS concentrations required to kill\n                    <jats:italic>S. aureus in vitro<\/jats:italic>\n                    are much higher than those found in the phagosome. We therefore hypothesized that sublethal ROS concentrations may play a role in\n                    <jats:italic>S. aureus<\/jats:italic>\n                    gene dysregulation and investigated the\n                    <jats:italic>in vitro<\/jats:italic>\n                    transcriptomic response of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    to sublethal concentrations of hydrogen peroxide (H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    ). A striking observation of these experiments was a coordinated and massive downregulation of genes involved in pyrimidine metabolism. Using transposon insertion mutants, we demonstrated that deletion of\n                    <jats:italic>carA<\/jats:italic>\n                    , a gene involved in pyrimidine synthesis, led to a significant growth defect and to an increased sensitivity of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    to added H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    . The phenotype of the\n                    <jats:italic>carA<\/jats:italic>\n                    mutant could be reversed through supplementation with the pyrimidine precursor uracil, or with a multicopy vector encoding\n                    <jats:italic>carA<\/jats:italic>\n                    . As opposed to the impact of ROS on extracellular survival,\n                    <jats:italic>carA<\/jats:italic>\n                    deletion did not affect the intracellular survival in neutrophils. Our results raise the possibility that ROS-dependent downregulation of pyrimidine metabolism might be a survival strategy of\n                    <jats:italic>S. aureus<\/jats:italic>\n                    , allowing colonization through intracellular survival, while decreasing the risk of killing the host through dampened extracellular growth.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2021.673985","type":"journal-article","created":{"date-parts":[[2021,9,7]],"date-time":"2021-09-07T09:04:10Z","timestamp":1631005450000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":39,"title":["Hydrogen Peroxide Affects Growth of S. aureus Through Downregulation of Genes Involved in Pyrimidine Biosynthesis"],"prefix":"10.3389","volume":"12","author":[{"given":"H\u00e9l\u00e8ne","family":"Buvelot","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myriam","family":"Roth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Jaquet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Lozkhin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana","family":"Renzoni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve-Julie","family":"Bonetti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Gaia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriane","family":"Laumay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mich\u00e9le","family":"Mollin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Jos\u00e9.","family":"Stasia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacques","family":"Schrenzel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrice","family":"Fran\u00e7ois","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl-Heinz","family":"Krause","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00079-16","article-title":"Hidden Staphylococcus Aureus Carriage: Overrated or Underappreciated","volume":"7","author":"van Belkum","year":"2016","journal-title":"mBio"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.02836.x","article-title":"Body Site Colonization in Patients With Community-Associated Methicillin-Resistant Staphylococcus Aureus and Other Types of S. 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