{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:26:55Z","timestamp":1785403615489,"version":"3.56.0"},"reference-count":86,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T00:00:00Z","timestamp":1763596800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2025,11,20]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      are the two pathogens that colonize the airway of cystic fibrosis patients. As patients age,\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      outcompetes\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      to become the predominant organism in the airway, which overlaps with worsening symptoms. This inverse correlation is partly due to the ability of\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      to secrete secondary metabolites and virulence factors that are antagonistic to the host cells and other bacteria present. Several of these secondary metabolites inhibit\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      respiration. SaeRS is a two-component regulatory system that promotes the transcription of numerous virulence genes in\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      . The transcription of SaeRS-regulated genes is decreased as a function of respiratory status. The accumulation of intracellular fatty acids also negatively impacts the activity of SaeRS. Incubation of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      with\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      cell-free conditioned culture medium decreased the transcriptional output of the SaeRS system. Further analyses using\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      mutant strains and chemical genetics determined that 2-heptyl-4-quinolone N-oxide (HQNO) was responsible for the SaeRS-dependent changes in gene regulation. Treatment with HQNO increased the abundance of cell-associated fatty acids. HQNO inhibits cell respiration, and the SaeRS system did not respond to HQNO treatment in a respiration-impaired\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      strain, which accumulates fatty acids. The data presented are consistent with a working model wherein treatment of\n                      <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                      with HQNO inhibits respiration, increasing free fatty acid accumulation, which negatively impacts SaeRS signaling. This results in decreased expression of the SaeRS regulon, which has significant roles in pathogenesis.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                        are often co-isolated from the airways of cystic fibrosis patients.\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        secretes non-essential metabolites that alter\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        physiology, providing\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        with a competitive advantage.\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        can adapt to the presence of these metabolites, but the genetic mechanisms used to sense these\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        -produced metabolites and\/or the induced physiological changes are largely unknown. The\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        SaeRS two-component regulatory system positively regulates the expression of various virulence factors, including toxins and proteases, that facilitate adaptation to and survival in hostile host environments. This study demonstrates that the\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        -produced respiratory toxin 2-heptyl-4-quinolone N-oxide inhibits respiration, decreasing the transcription of SaeRS-regulated genes and thereby decreasing virulence factor production. These findings could be exploited to decrease the ability of\n                        <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                        to express virulence factors in various infection settings.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jb.00395-25","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T13:03:25Z","timestamp":1759928605000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["<i>Pseudomonas aeruginosa-<\/i>\n                    secreted respiratory toxin HQNO triggers fatty acid accumulation in respiring\n                    <i>Staphylococcus aureus,<\/i>\n                    decreasing SaeRS-dependent transcriptional 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