{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T00:11:17Z","timestamp":1747181477877,"version":"3.40.5"},"reference-count":39,"publisher":"Microbiology Society","issue":"12","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,20]]},"abstract":"<jats:p>Intravenous gallium nitrate therapy is a novel therapeutic strategy deployed to combat chronic <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> biofilm infections in the lungs of cystic fibrosis (CF) patients by interfering with iron (Fe<jats:sup>3+<\/jats:sup>) uptake. The therapy is a source of Ga<jats:sup>3+<\/jats:sup>, which competes with Fe<jats:sup>3+<\/jats:sup> for siderophore binding, subsequently disrupting iron metabolism and inhibiting biofilm proliferation <jats:italic>in vivo<\/jats:italic>. It was recently demonstrated that the <jats:italic>\n                     <jats:named-content content-type=\"genus\">\n                        <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/doi.org\/10.1601\/nm.2552\" xlink:type=\"simple\">Pseudomonas<\/jats:ext-link>\n                     <\/jats:named-content>\n                  <\/jats:italic> quinolone signal (PQS) can chelate Fe<jats:sup>3+<\/jats:sup> to assist in bacterial iron uptake. However, it is unknown whether exogenous gallium also targets [Fe(PQS)<jats:sub>3<\/jats:sub>] uptake, which, in turn, would extend the mechanism of gallium therapy beyond siderophore competition, potentially supporting use of the therapy against <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> mutants deficient in siderophore uptake proteins. To that end, the thermodynamic feasibility of iron-for-gallium cation exchange into [Fe(PQS)<jats:sub>3<\/jats:sub>] was evaluated using quantum chemical density functional theory (DFT) modelling and verified experimentally using <jats:sup>1<\/jats:sup>H nuclear magnetic resonance (NMR). We demonstrate here that Ga<jats:sup>3+<\/jats:sup> can strongly bind to three PQS molecules and, furthermore, displace and substitute Fe<jats:sup>3+<\/jats:sup> from the native chelate pocket within PQS complexes, through a Trojan horse mechanism, retaining the key structural features present within the native ferric complex. As such, [Fe(PQS)<jats:sub>3<\/jats:sub>] complexes, in addition to ferric\u2013siderophore complexes, represent another target for gallium therapy.<\/jats:p>","DOI":"10.1099\/mic.0.001422","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T16:17:08Z","timestamp":1703089028000},"source":"Crossref","is-referenced-by-count":1,"title":["Atomistic modelling and NMR studies reveal that gallium can target the ferric PQS uptake system in P. aeruginosa biofilms"],"prefix":"10.1099","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8953-7378","authenticated-orcid":false,"given":"Oliver J.","family":"Hills","sequence":"first","affiliation":[{"name":"School of Food Science and Nutrition, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac O.K.","family":"Noble","sequence":"additional","affiliation":[{"name":"School of Food Science and Nutrition, University of Leeds, 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