{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T05:49:31Z","timestamp":1782280171559,"version":"3.54.5"},"posted":{"date-parts":[[2025,3,12]]},"group-title":"Microbiology","reference-count":64,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:00:00Z","timestamp":1741737600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                  and\n                  <jats:italic>Staphylococcus aureus<\/jats:italic>\n                  are primary bacterial pathogens isolated from the airways of cystic fibrosis patients.\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  produces secondary metabolites that negatively impact the fitness of\n                  <jats:italic>S. aureus,<\/jats:italic>\n                  allowing\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  to become the most prominent bacterium when the species are co-cultured. Some of these metabolites inhibit\n                  <jats:italic>S. aureus<\/jats:italic>\n                  respiration. SrrAB is a staphylococcal two-component regulatory system (TCRS) that responds to alterations in respiratory status and helps\n                  <jats:italic>S. aureus<\/jats:italic>\n                  transition between fermentative and respiratory metabolisms. We used\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  mutant strains and chemical genetics to demonstrate that\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  secondary metabolites, HQNO in particular, inhibit\n                  <jats:italic>S. aureus<\/jats:italic>\n                  respiration, resulting in modified SrrAB stimulation. Metabolomic analyses found 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, had altered activity upon HQNO treatment. The presence of SrrAB increased fitness when cultured with HQNO and increased survival when challenged with\n                  <jats:italic>P. aeruginosa. S. aureus<\/jats:italic>\n                  strains with a decreased ability to maintain redox homeostasis via fermentation had decreased fitness when challenged with HQNO and decreased survival when challenged with\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  . These findings led to a model wherein\n                  <jats:italic>P. aeruginosa<\/jats:italic>\n                  secreted HQNO inhibits\n                  <jats:italic>S. aureus<\/jats:italic>\n                  respiration, stimulating SrrAB, which promotes fitness and survival by increasing carbon flux through fermentative pathways to maintain redox homeostasis.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Importance<\/jats:title>\n                  <jats:p>\n                    Cystic fibrosis (CF) is a hereditary respiratory disease that predisposes patients to bacterial infections, primarily caused by\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    and\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    .\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    excreted secondary metabolites decrease\n                    <jats:italic>S. aureus<\/jats:italic>\n                    fitness during co-infection, ultimately eliminating it. The genetic mechanisms that\n                    <jats:italic>S. aureus<\/jats:italic>\n                    uses to detect and respond to these metabolites are unknown. The\n                    <jats:italic>S. aureus<\/jats:italic>\n                    SrrAB two-component regulatory system senses flux through respiratory pathways and increases transcription of genes utilized for adaption to low-respiration environments. This study demonstrates that SrrAB responds to the\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    -produced respiratory toxin HQNO and responds by increasing fermentation increasing competition. This study describes interactions between these two bacterial pathogens, which could be exploited to decrease pathogen burden in individuals living with cystic fibrosis.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.12.642861","type":"posted-content","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T12:54:44Z","timestamp":1741870484000},"source":"Crossref","is-referenced-by-count":2,"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":"10.64898","author":[{"given":"Franklin","family":"Roman-Rodriguez","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, 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, Newark, NJ 07103, 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, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7721-3926","authenticated-orcid":false,"given":"Jeffrey M.","family":"Boyd","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026041100212366000_2025.03.12.642861v1.1","doi-asserted-by":"publisher","DOI":"10.1186\/1465-9921-4-8"},{"key":"2026041100212366000_2025.03.12.642861v1.2","unstructured":"Foundation CF . 2021. 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