{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T17:18:04Z","timestamp":1785863884311,"version":"3.56.0"},"reference-count":77,"publisher":"Microbiology Society","issue":"8","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000897","name":"Cystic Fibrosis Foundation","doi-asserted-by":"crossref","award":["WARGO25G0"],"award-info":[{"award-number":["WARGO25G0"]}],"id":[{"id":"10.13039\/100000897","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:p>\n                    Antimicrobial resistance is an increasing threat to global health. However, there is a limited set of antibiotics that are effective against drug-resistant Gram-negative bacteria like\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    . One strategy to enhance the efficacy and longevity of existing antibiotics is by combining them with non-traditional antimicrobial adjuvants. Here, we examined if the host-derived antimicrobial lipid sphingosine could enhance the efficacy of a panel of antibiotics against\n                    <jats:italic>P. aeruginosa in vitro<\/jats:italic>\n                    . We found that sphingosine displayed strong synergy with the polymyxin antibiotics, polymyxin B and colistin, to inhibit growth of and kill\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    but did not significantly alter the efficacy of other tested antibiotic classes. The addition of sphingosine reduced the MIC of polymyxin B and colistin from 0.5 to 0.031 \u00b5g ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    and 8 to 0.5 \u00b5g ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    , respectively. This combination of sphingosine and polymyxin B synergized to inhibit the growth and survival of\n                    <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n                    , as well as clinically isolated of\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    . In addition to sphingosine, we found that the sphingoid bases sphinganine (dihydrosphingosine) and phytosphingosine also enhanced the activity of polymyxins. Overall, these findings demonstrate that sphingosine is a potent adjuvant for polymyxins and that the sphingosine\u2013polymyxin combination is capable of killing\n                    <jats:italic>P. aeruginosa<\/jats:italic>\n                    and\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    while using relatively low concentrations of polymyxin. This study may help in the development of new antimicrobial therapies for the treatment of Gram-negative bacterial infections.\n                  <\/jats:p>","DOI":"10.1099\/mic.0.001743","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:16:39Z","timestamp":1785860199000},"source":"Crossref","is-referenced-by-count":0,"title":["Sphingosine synergizes with polymyxin antibiotics against Pseudomonas aeruginosa and Klebsiella pneumoniae"],"prefix":"10.1099","volume":"172","author":[{"given":"Jacob R.","family":"Mackinder","sequence":"first","affiliation":[{"name":"Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, USA"},{"name":"Department of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Quinlan","sequence":"additional","affiliation":[{"name":"Cellular, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, USA"},{"name":"Department of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5659-749X","authenticated-orcid":false,"given":"Matthew J.","family":"Wargo","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, Larner College of Medicine, University of Vermont, Burlington, 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