{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:45:09Z","timestamp":1785415509115,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the European Union","award":["ECS00000017"],"award-info":[{"award-number":["ECS00000017"]}]},{"name":"the European Union","award":["CUP I53C22000780001"],"award-info":[{"award-number":["CUP I53C22000780001"]}]},{"award":["ECS00000017"],"award-info":[{"award-number":["ECS00000017"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]},{"award":["CUP I53C22000780001"],"award-info":[{"award-number":["CUP I53C22000780001"]}],"id":[{"id":"https:\/\/ror.org\/019w4f821","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Auranofin (AF), an FDA-approved drug for rheumatoid arthritis, exhibits strong antibacterial activity against Gram-positive bacteria, while Gram-negative species remain largely tolerant. This study assessed the antimicrobial activity of AF and three analogues against clinically relevant Gram-negative pathogens and explored tolerance mechanisms in Pseudomonas aeruginosa. Broth microdilution assays were performed on reference strains and clinical isolates of Escherichia coli, Klebsiella pneumoniae, and P. aeruginosa. Synergy studies with the most active analogue, PEt3AuCl (AF-Cl), were conducted against P. aeruginosa using polymyxin B (PMB), two efflux-pump inhibitors, and two glutathione (GSH) depletors. Gold compounds showed MICs between 4 and &gt;64 \u00b5g\/mL, with AF-Cl displaying the highest activity. AF-Cl activity was markedly enhanced by PMB and efflux-pump inhibitors, indicating that outer membrane permeability and efflux contribute to tolerance. Additionally, GSH depletion significantly potentiated AF-Cl, implicating redox homeostasis in resistance. Overall, AF-Cl shows potential against Gram-negative bacteria when combined with agents targeting membrane integrity, efflux systems, or redox balance, supporting combinatorial strategies to overcome resistance in P. aeruginosa and related pathogens.<\/jats:p>","DOI":"10.3390\/ijms27104610","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T12:06:07Z","timestamp":1779365167000},"page":"4610","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergy Between the Auranofin Analogue PEt3AuCl and Membrane Disruptors, Efflux-Pump Blockers, and Glutathione-Depletors Uncovers Tolerance Pathways in Pseudomonas aeruginosa"],"prefix":"10.3390","volume":"27","author":[{"given":"Beatrice","family":"Amato","sequence":"first","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7747-8200","authenticated-orcid":false,"given":"Diletta","family":"Mazzantini","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9387-9215","authenticated-orcid":false,"given":"Jos\u00e9 Aleixo","family":"de Azevedo-Fran\u00e7a","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Florence, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppantonio","family":"Maisetta","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6863-1384","authenticated-orcid":false,"given":"Emilia","family":"Ghelardi","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4358-5294","authenticated-orcid":false,"given":"Semih","family":"Esin","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9490-8014","authenticated-orcid":false,"given":"Luigi","family":"Messori","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Florence, 50019 Florence, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-2385","authenticated-orcid":false,"given":"Giovanna","family":"Batoni","sequence":"additional","affiliation":[{"name":"Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Tamma, P.D., Heil, E.L., Justo, J.A., Mathers, A.J., Satlin, M.J., and Bonomo, R.A. 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