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Staphylococcus aureus uses the ferric uptake transcriptional regulator (Fur) to sense titers of cytosolic Fe. Upon Fe depletion, apo-Fur relieves transcriptional repression of genes utilized for Fe uptake. We demonstrate that an S. aureus \u0394fur mutant has decreased expression of acnA, which codes for the Fe-dependent enzyme aconitase. This prevents the \u0394fur mutant from growing with amino acids as sole carbon and energy sources. We used a suppressor screen to exploit this phenotype and determined that a mutation that decreases the transcription of isrR, which produces a regulatory RNA, increased acnA expression, thereby enabling growth. Directed mutation of bases predicted to facilitate the interaction between the acnA transcript and IsrR, decreased the ability of IsrR to control acnA expression in vivo and IsrR bound to the acnA transcript in vitro. IsrR also bound transcripts coding the alternate tricarboxylic acid cycle proteins sdhC, mqo, citZ and citM. Whole-cell metal analyses suggest that IsrR promotes Fe uptake and increases intracellular Fe not ligated by macromolecules. Lastly, we determined that Fur and IsrR promote infection using murine skin and acute pneumonia models.<\/jats:p>","DOI":"10.1093\/nar\/gkae1243","type":"journal-article","created":{"date-parts":[[2024,12,4]],"date-time":"2024-12-04T15:28:23Z","timestamp":1733326103000},"source":"Crossref","is-referenced-by-count":21,"title":["The\n                    <i>Staphylococcus aureus<\/i>\n                    non-coding RNA IsrR regulates TCA cycle activity and virulence"],"prefix":"10.1093","volume":"53","author":[{"given":"Gustavo","family":"Rios-Delgado","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers, the State University of New Jersey , 76 Lipman Dr,\u00a0 New Brunswick , NJ 08901 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aubrey\u00a0K G","family":"McReynolds","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center , 3901 Rainbow Boulevard, Kansas City , KS 66160 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma\u00a0A","family":"Pagella","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center , 3901 Rainbow Boulevard, Kansas City , KS 66160 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javiera","family":"Norambuena","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers, the State University of New Jersey , 76 Lipman Dr,\u00a0 New Brunswick , NJ 08901 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul","family":"Briaud","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Ohio University , 7 Depot St,\u00a0 Athens , OH 45701 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers, the State University of New Jersey , 76 Lipman Dr,\u00a0 New Brunswick , NJ 08901 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew\u00a0J","family":"Munneke","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , 1211 Medical Center Drive,\u00a0 Nashville , TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School , 185 South Orange Avenue,\u00a0 Newark , NJ 07103 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugo","family":"Racine","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, Architecture et R\u00e9activit\u00e9 de l\u2019ARN, UPR9002 , 15 rue Ren\u00e9 Descartes,\u00a0 Strasbourg 67000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronan\u00a0K","family":"Carroll","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Ohio University , 7 Depot St,\u00a0 Athens , OH 45701 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehud","family":"Zelzion","sequence":"additional","affiliation":[{"name":"Office of Advanced Research Computing, Rutgers University , 96 Frelinghuysen Road , Piscataway , NJ 08854 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Skaar","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center , 1211 Medical Center Drive,\u00a0 Nashville , TN 37232 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey\u00a0L","family":"Bose","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center , 3901 Rainbow Boulevard, Kansas City , KS 66160 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane","family":"Parker","sequence":"additional","affiliation":[{"name":"Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School , 185 South Orange Avenue,\u00a0 Newark , NJ 07103 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Lalaouna","sequence":"additional","affiliation":[{"name":"Universit\u00e9 de Strasbourg, CNRS, Architecture et R\u00e9activit\u00e9 de l\u2019ARN, UPR9002 , 15 rue Ren\u00e9 Descartes,\u00a0 Strasbourg 67000 ,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7721-3926","authenticated-orcid":false,"given":"Jeffrey\u00a0M","family":"Boyd","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers, the State University of New Jersey , 76 Lipman Dr,\u00a0 New Brunswick , NJ 08901 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,19]]},"reference":[{"key":"2025030421263747900_B1","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1128\/CMR.00134-14","article-title":"Staphylococcus aureus infections: epidemiology, pathophysiology, clinical manifestations, and management","volume":"28","author":"Tong","year":"2015","journal-title":"Clin. 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