{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T02:21:15Z","timestamp":1791512475964,"version":"4.3.4"},"reference-count":46,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,8,7]],"date-time":"2024-08-07T00:00:00Z","timestamp":1722988800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["P01-AI083214"],"award-info":[{"award-number":["P01-AI083214"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,8,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              In this study, we showed that phenazine-1 carboxylic acid (PCA) of\n              <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n              induced the expression of Tet38 efflux pump triggering\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              resistance to tetracycline and phenazines. Exposure of\n              <jats:italic>S. aureus<\/jats:italic>\n              RN6390 to supernatants of\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              PA14 and its pyocyanin (PYO)-deficient mutants showed that\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              non-PYO phenazines could induce the expression of Tet38 efflux pump. Direct exposure of RN6390 to PCA compound at 0.25\u00d7 MIC led to a five-fold increase in\n              <jats:italic>tet38<\/jats:italic>\n              transcripts. Expression of Tet38 protein was identified through confocal microscopy using RN6390(pRN-\n              <jats:italic>tet38<\/jats:italic>\n              p-\n              <jats:italic>yfp<\/jats:italic>\n              ) that expressed YFP under control of the\n              <jats:italic>tet38<\/jats:italic>\n              promoter by PCA at 0.25\u00d7 MIC. The MICs of PCA of a Tet38-overexpressor and a\n              <jats:italic>\u0394tet38<\/jats:italic>\n              mutant showed a three-fold increase and a two-fold decrease, respectively, compared with that of wild-type. Pre-exposure of RN6390 to PCA (0.25\u00d7 MIC) for 1 hour prior to addition of tetracycline (1\u00d7 or 10\u00d7 MIC) improved bacteria viability of 1.5-fold and 2.6-fold, respectively, but addition of NaCl 7% together with tetracycline at 10\u00d7 MIC reduced the number of viable PCA-exposed RN6390 of a 2.0-log\n              <jats:sub>10<\/jats:sub>\n              CFU\/mL. The transcript levels of\n              <jats:italic>tetR21<\/jats:italic>\n              , a repressor of\n              <jats:italic>tet38<\/jats:italic>\n              , decreased and increased two-fold in the presence of PCA and NaCl, respectively, suggesting that the effects of PCA and NaCl on\n              <jats:italic>tet38<\/jats:italic>\n              production occurred through TetR21 expression. These data suggest that PCA-induced Tet38 protects\n              <jats:italic>S. aureus<\/jats:italic>\n              against tetracycline during coinfection with\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              ; however, induced\n              <jats:italic>tet38<\/jats:italic>\n              -mediated\n              <jats:italic>S. aureus<\/jats:italic>\n              resistance to tetracycline is reversed by NaCl 7%, a nebulized treatment used to enhance sputum mobilization in CF patients.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.00636-24","type":"journal-article","created":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T13:00:26Z","timestamp":1721394026000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":6,"title":["Phenazine-1 carboxylic acid of\n            <i>Pseudomonas aeruginosa<\/i>\n            induces the expression of\n            <i>Staphylococcus aureus<\/i>\n            Tet38 MDR efflux pump and mediates resistance to phenazines and antibiotics"],"prefix":"10.1128","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3275-4360","authenticated-orcid":true,"given":"Q. C.","family":"Truong-Bolduc","sequence":"first","affiliation":[{"name":"Infectious Diseases Division and Medical Services, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Y.","family":"Wang","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division and Medical Services, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. G.","family":"Lawton","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cystic Fibrosis Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"Brown Harding","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division and Medical Services, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. M.","family":"Yonker","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Cystic Fibrosis Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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