{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:37:49Z","timestamp":1787225869853,"version":"build-2736575974"},"reference-count":62,"publisher":"Microbiology Society","issue":"7","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"crossref","award":["BB\/K019600\/1"],"award-info":[{"award-number":["BB\/K019600\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"crossref","award":["BB\/V509243\/1"],"award-info":[{"award-number":["BB\/V509243\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"crossref","award":["BB\/S507106\/1"],"award-info":[{"award-number":["BB\/S507106\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Chief Scientist Office","award":["TCS\/16\/24"],"award-info":[{"award-number":["TCS\/16\/24"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,7,29]]},"abstract":"<jats:p>Lysophosphatidic acid (LPA) occurs naturally in inflammatory exudates and has previously been shown to increase the susceptibility of <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.2553\" xlink:type=\"simple\">Pseudomonas aeruginosa<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic> to \u03b2-lactam antibiotics whilst concomitantly reducing accumulation of the virulence factors pyoverdine and elastase. Here it is demonstrated that LPA can also exert inhibitory effects upon pyocyanin production in <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.2553\" xlink:type=\"simple\">P. aeruginosa<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic>, as well as influencing susceptibility to a wide range of chemically diverse non \u03b2-lactam antimicrobials. Most strikingly, LPA markedly antagonizes the effect of the polycationic antibiotics colistin and tobramycin at a concentration of 250\u2009\u00b5g\u2009ml<jats:sup>\u22121<\/jats:sup> whilst conversely enhancing their efficacy at the lower concentration of 8.65 \u00b5g\u2009ml<jats:sup>\u22121<\/jats:sup>, approximating the maximal physiological concentrations found in inflammatory exudates. Transcriptomic responses of the virulent strain UCBPP-PA14 to LPA were analysed using RNA-sequencing along with BioLog phenoarrays and whole cell assays in attempts to delineate possible mechanisms underlying these effects. The results strongly suggest involvement of LPA-induced carbon catabolite repression together with outer-membrane (OM) stress responses whilst raising questions about the effect of LPA upon other <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.2553\" xlink:type=\"simple\">P. aeruginosa<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic> virulence factors including type III secretion. This could have clinical relevance as it suggests that endogenous LPA may, at concentrations found <jats:italic>in vivo<\/jats:italic>, differentially modulate antibiotic susceptibility of <jats:italic>\n                     <jats:named-content content-type=\"species\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.2553\" xlink:type=\"simple\">P. aeruginosa<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic> whilst simultaneously regulating expression of virulence factors, thereby influencing host\u2013pathogen interactions during infection. The possibility of applying exogenous LPA locally as an enhancer of select antibiotics merits further investigation.<\/jats:p>","DOI":"10.1099\/mic.0.001179","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T14:16:05Z","timestamp":1657203365000},"source":"Crossref","is-referenced-by-count":3,"title":["Host lysolipid differentially modulates virulence factor expression and antimicrobial susceptibility in Pseudomonas aeruginosa"],"prefix":"10.1099","volume":"168","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2070-8316","authenticated-orcid":false,"given":"James C.","family":"McSorley","sequence":"first","affiliation":[{"name":"Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1632-0944","authenticated-orcid":false,"given":"Alison 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