{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T23:00:51Z","timestamp":1785452451656,"version":"3.56.0"},"posted":{"date-parts":[[2026,7,27]]},"group-title":"Microbiology","reference-count":29,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"NIH-NIAID","award":["AI176245"],"award-info":[{"award-number":["AI176245"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,27]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  The human opportunistic pathogen\n                  <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                  produces copious quantities of the secondary metabolite pyocyanin (PYO). PYO has recently been shown to interact with the aryl hydrocarbon receptor (AhR), a transcription factor controlling expression of a number of genes, including the cytochrome P450 CYP1A family involved in fluoroquinolone antibiotic clearance. In this study, we investigated whether\n                  <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                  could influence the metabolism of ciprofloxacin through human\n                  <jats:italic>CYP1A2<\/jats:italic>\n                  induction. Primary human hepatocytes were exposed to 1-100 \u03bcM PYO, with high concentrations resulting in apparent cytotoxicity. Treatment with 5 \u00b5M PYO led to a 6.2-fold change in\n                  <jats:italic>CYP1A2<\/jats:italic>\n                  mRNA and a 3.6-fold increase in oxociprofloxacin metabolite formation. Our results suggest that sub-toxic concentrations of PYO induce\n                  <jats:italic>CYP1A2<\/jats:italic>\n                  expression and increase ciprofloxacin metabolism, which could lead to sub-efficacious antibiotic concentrations and further drive resistance. This finding directs us to a novel mechanism by which\n                  <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                  may escape antimicrobial therapy by hijacking host xenobiotic metabolism pathways.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>GRAPHICAL ABSTRACT<\/jats:title>\n                  <jats:fig id=\"ufig1\" position=\"float\" orientation=\"portrait\" fig-type=\"figure\">\n                    <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"740721v1_ufig1\" position=\"float\" orientation=\"portrait\"\/>\n                  <\/jats:fig>\n                <\/jats:sec>","DOI":"10.64898\/2026.07.25.740721","type":"posted-content","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:15:12Z","timestamp":1785215712000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>Pseudomonas aeruginosa<\/i>\n                  co-opts host antibiotic metabolism by pyocyanin induction of cytochrome P450 enzymes"],"prefix":"10.64898","author":[{"given":"Emily G.","family":"Gracey","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado, Aurora, Colorado 80045, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvie E.","family":"Kandel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado, Aurora, Colorado 80045, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0794-2263","authenticated-orcid":false,"given":"Jed N.","family":"Lampe","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Skaggs School of Pharmacy, University of Colorado, Aurora, Colorado 80045, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026073015501055000_2026.07.25.740721v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.VMBF-0027-2015"},{"key":"2026073015501055000_2026.07.25.740721v1.2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.VMBF-0017-2015"},{"key":"2026073015501055000_2026.07.25.740721v1.3","doi-asserted-by":"publisher","DOI":"10.21315\/mjms2022.29.1.2"},{"key":"2026073015501055000_2026.07.25.740721v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-021-00620-w"},{"key":"2026073015501055000_2026.07.25.740721v1.5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1550724"},{"key":"2026073015501055000_2026.07.25.740721v1.6","doi-asserted-by":"publisher","DOI":"10.1007\/s11274-024-03889-0"},{"key":"2026073015501055000_2026.07.25.740721v1.7","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.56.9.2515-2517.1988"},{"key":"2026073015501055000_2026.07.25.740721v1.8","doi-asserted-by":"publisher","DOI":"10.1038\/nature13684"},{"key":"2026073015501055000_2026.07.25.740721v1.9","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70426"},{"key":"2026073015501055000_2026.07.25.740721v1.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0125-8"},{"key":"2026073015501055000_2026.07.25.740721v1.11","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaw1629"},{"key":"2026073015501055000_2026.07.25.740721v1.12","doi-asserted-by":"crossref","unstructured":"Gotoh, S. ; Ohno, M. ; Yoshinari, K. ; Negishi, M. ; Kawajiri, K. 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