{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:59:20Z","timestamp":1790085560455,"version":"4.0.1"},"reference-count":27,"publisher":"American Society for Microbiology","license":[{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T00:00:00Z","timestamp":1790035200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                      is a major opportunistic pathogen responsible for chronic lung infections in cystic fibrosis (CF) patients, contributing significantly to morbidity and mortality. In this study, we investigated the synergistic activity of colistin combined with two natural stilbenoids, pterostilbene and (\u00b1)-\n                      <jats:italic toggle=\"yes\">trans<\/jats:italic>\n                      -\u03b5-viniferin, against clinical\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      isolates from CF patients. Synergy was assessed through minimum inhibitory concentration (MIC) determination and time\u2013kill assays. The combination of colistin with pterostilbene reduced colistin MIC values in all tested strains, with the strongest effect observed in a colistin-resistant isolate (eightfold reduction, fractional inhibitory concentration index = 0.188). Time\u2013kill assays confirmed enhanced bactericidal activity, with faster and more effective bacterial killing compared to colistin alone. According to the known mechanism of action of colistin, medium supplementation with purified lipopolysaccharide (LPS) reduced colistin activity on\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      . Medium supplementation with stilbenoids partially restored colistin activity, reducing the negative effect of LPS. Flow cytometry analyses showed increased membrane permeability in the presence of the combination of colistin and pterostilbene, whereas elevated concentrations of divalent cations reduced this effect, highlighting the role of electrostatic interactions in colistin\/pterostilbene membrane damage. Overall, these findings suggest that pterostilbene acts as a colistin adjuvant\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      , enhancing its antimicrobial activity against\n                      <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                      through a mechanism involving cell membrane damage.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        <jats:italic toggle=\"yes\">Pseudomonas aeruginosa<\/jats:italic>\n                        is a major cause of chronic lung infections in cystic fibrosis patients and is increasingly difficult to treat because of antibiotic resistance. Colistin remains one of the few effective last-line therapies against this bacterial pathogen, but its clinical use is limited by severe dose-dependent toxicity. In this study, we show that pterostilbene, a natural stilbenoid compound, enhances\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        the activity of colistin against clinical\n                        <jats:italic toggle=\"yes\">P. aeruginosa<\/jats:italic>\n                        isolates. The combination improved colistin efficacy, increased membrane damage, and partially overcame lipopolysaccharide-mediated reduction of colistin activity. Importantly, these effects were achieved using low concentrations of pterostilbene under the experimental conditions tested.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.01534-26","type":"journal-article","created":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T13:00:09Z","timestamp":1790082009000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Synergistic activity of colistin and stilbenoids against\n                    <i>Pseudomonas aeruginosa<\/i>\n                    clinical isolates"],"prefix":"10.1128","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3817-0457","authenticated-orcid":true,"given":"Nicola","family":"Mangieri","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Annunziata","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2042-608X","authenticated-orcid":true,"given":"Elio","family":"Rossi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biosciences, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerio","family":"Baldelli","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biosciences, University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-3348","authenticated-orcid":true,"given":"Andrea","family":"Pinto","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Food, Environmental and Nutritional Sciences (DeFENS), University of Milan","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina","family":"Dallavalle","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00wjc7c48","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Food, Environmental and 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