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Some of these metabolites inhibit\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      respiration. SrrAB is a staphylococcal two-component regulatory system (TCRS) that responds to alterations in respiratory status to help\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      transition between fermentative and respiratory metabolisms. Using\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      mutant strains and chemical genetics, we established that\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      secondary metabolites, 2-heptyl-4-quinolone N-oxide (HQNO) in particular, inhibit\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      respiration, resulting in decreased SrrAB transcriptional output. Metabolomic analyses demonstrated that the ratio of NAD\n                      <jats:sup>+<\/jats:sup>\n                      to NADH increased upon prolonged culture with HQNO. Consistent with this, the activity of the Rex transcriptional regulator, which senses and responds to alterations in the NAD\n                      <jats:sup>+<\/jats:sup>\n                      \/NADH ratio, repressed\n                      <jats:italic toggle=\"yes\">srrAB<\/jats:italic>\n                      promoter activity upon HQNO treatment. The presence of SrrAB increased fitness when cultured with HQNO and enhanced survival when challenged with\n                      <jats:italic toggle=\"yes\">P. aeruginosa. S. aureus<\/jats:italic>\n                      strains with reduced ability to maintain redox homeostasis via fermentation had decreased fitness when challenged with HQNO and lower survival when challenged with\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      . These findings led to a model wherein\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      secreted HQNO inhibits\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      respiration, resulting in manipulation of the redox status in both the membrane and cytoplasm, altering the transcriptional activities of SrrAB and Rex, which promote fitness and survival by increasing carbon flux through fermentative pathways to maintain redox homeostasis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      Cystic fibrosis is a hereditary respiratory disease that predisposes patients to bacterial infections, often caused by\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      . Secondary metabolites excreted by\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      decrease\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      fitness during co-infection, ultimately eliminating it. The regulatory systems and mechanisms that\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      uses to detect and respond to these metabolites are unknown. The data presented demonstrate that two regulatory systems that are stimulated by alterations in membrane or cytosolic redox status respond to the\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      -produced respiratory toxin 2-heptyl-4-quinolone N-oxide (HQNO) by increasing transcription of genes utilized for fermentation, thereby promoting fitness. This study describes interactions between these two bacterial pathogens that could be exploited to decrease pathogen burden in individuals living with cystic fibrosis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00101-25","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T13:01:08Z","timestamp":1760965268000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["An effective response to respiratory inhibition by a\n                    <i>Pseudomonas aeruginosa<\/i>\n                    excreted quinoline promotes\n                    <i>Staphylococcus aureus<\/i>\n                    fitness and survival in co-culture"],"prefix":"10.1128","volume":"207","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2419-5984","authenticated-orcid":false,"given":"Franklin","family":"Roman-Rodriguez","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05vt9qd57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey","place":["New Brunswick, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nupur","family":"Tyagi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05vt9qd57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey","place":["New Brunswick, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jisun","family":"Kim","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/014ye1258","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dane","family":"Parker","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/014ye1258","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Pathology, Immunology and Laboratory Medicine, Center for Immunity and Inflammation, Rutgers New Jersey Medical School","place":["Newark, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7721-3926","authenticated-orcid":true,"given":"Jeffrey M.","family":"Boyd","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05vt9qd57","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey","place":["New Brunswick, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-4-8"},{"key":"e_1_3_4_3_2","unstructured":"Foundation CF. 2021. 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