{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T08:46:27Z","timestamp":1790066787462,"version":"4.0.1"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"14","license":[{"start":{"date-parts":[[2018,7,15]],"date-time":"2018-07-15T00:00:00Z","timestamp":1531612800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103638"],"award-info":[{"award-number":["P20GM103638"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R24GM111385"],"award-info":[{"award-number":["R24GM111385"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA211720"],"award-info":[{"award-number":["R01 CA211720"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["S10RR024664"],"award-info":[{"award-number":["S10RR024664"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["1625923"],"award-info":[{"award-number":["1625923"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"HHS | National Institutes of Health","doi-asserted-by":"publisher","award":["RO1 AI125529"],"award-info":[{"award-number":["RO1 AI125529"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["MCB1615767"],"award-info":[{"award-number":["MCB1615767"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Bacteriol"],"published-print":{"date-parts":[[2018,7,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content content-type=\"genus-species\">Burkholderia pseudomallei<\/jats:named-content>\n            , the causative agent of melioidosis, encodes almost a dozen predicted polyketide (PK) biosynthetic gene clusters. Many of these are regulated by LuxR-I-type acyl-homoserine (AHL) quorum-sensing systems. One of the PK gene clusters, the\n            <jats:italic>mal<\/jats:italic>\n            gene cluster, is conserved in the close relative\n            <jats:named-content content-type=\"genus-species\">Burkholderia thailandensis<\/jats:named-content>\n            . The\n            <jats:italic>B. thailandensis mal<\/jats:italic>\n            genes code for the cytotoxin malleilactone and are regulated by a genetically linked LuxR-type transcription factor, MalR. Although AHLs typically interact with LuxR-type proteins to modulate gene transcription, the\n            <jats:named-content content-type=\"genus-species\">B. thailandensis<\/jats:named-content>\n            MalR does not appear to be an AHL receptor. Here, we characterize the\n            <jats:italic>mal<\/jats:italic>\n            genes and MalR in\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            . We use chemical analyses to demonstrate that the\n            <jats:italic>B. pseudomallei mal<\/jats:italic>\n            genes code for malleilactone. Our results show that MalR and the\n            <jats:italic>mal<\/jats:italic>\n            genes contribute to the ability of\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            to kill\n            <jats:named-content content-type=\"genus-species\">Caenorhabditis elegans<\/jats:named-content>\n            . In\n            <jats:named-content content-type=\"genus-species\">B. thailandensis<\/jats:named-content>\n            , antibiotics like trimethoprim can activate MalR by driving transcription of the\n            <jats:italic>mal<\/jats:italic>\n            genes, and we demonstrate that some of the same antibiotics induce expression of\n            <jats:italic>B. pseudomallei malR<\/jats:italic>\n            . We also demonstrate that\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            MalR does not respond directly to AHLs. Our results suggest that MalR is indirectly repressed by AHLs, possibly through a repressor, ScmR. We further show that malleilactone is a\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            virulence factor and provide the foundation for understanding how malleilactone contributes to the pathology of melioidosis infections.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Many bacterially produced polyketides are cytotoxic to mammalian cells and are potentially important contributors to pathogenesis during infection. We are interested in the polyketide gene clusters present in\n            <jats:named-content content-type=\"genus-species\">Burkholderia pseudomallei<\/jats:named-content>\n            , which causes the often-fatal human disease melioidosis. Using knowledge gained by studies in the close relative\n            <jats:named-content content-type=\"genus-species\">Burkholderia thailandensis<\/jats:named-content>\n            , we show that one of the\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            polyketide biosynthetic clusters produces a cytotoxic polyketide, malleilactone. Malleilactone contributes to\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            virulence in a\n            <jats:named-content content-type=\"genus-species\">Caenorhabditis elegans<\/jats:named-content>\n            infection model and is regulated by an orphan LuxR family quorum-sensing transcription factor, MalR. Our studies demonstrate that malleilactone biosynthesis or MalR could be new targets for developing therapeutics to treat melioidosis.\n          <\/jats:p>","DOI":"10.1128\/jb.00008-18","type":"journal-article","created":{"date-parts":[[2018,5,3]],"date-time":"2018-05-03T09:17:41Z","timestamp":1525339061000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":37,"title":["Malleilactone Is a Burkholderia pseudomallei Virulence Factor Regulated by Antibiotics and Quorum Sensing"],"prefix":"10.1128","volume":"200","author":[{"given":"Jennifer R.","family":"Klaus","sequence":"first","affiliation":[{"name":"Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Deay","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Neuenswander","sequence":"additional","affiliation":[{"name":"Chemical Methodologies and Library Development Legacy, University of Kansas, Lawrence, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wyatt","family":"Hursh","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhe","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, University of Kansas, Lawrence, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiffany","family":"Bouddhara","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, University of Kansas, Lawrence, Kansas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Todd 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