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New strategies, such as membrane-targeting molecules acting as adjuvants, aim to enhance antibiotic effectiveness and combat resistance. RW01, a cyclic peptide with low antimicrobial activity, was selected as an adjuvant to enhance drug efficacy through membrane permeabilization. RW01\u2019s activity was evaluated via antimicrobial susceptibility testing in combination with existing antibiotics on 10\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              strains and analog synthesis. Synergy was assessed using checkerboard assays, and one-step mutants were generated to identify altered pathways through whole-genome sequencing and variant analysis. Permeabilizing activity was studied using flow cytometry and real-time fluorescence measurement.\n              <jats:italic>In vivo<\/jats:italic>\n              toxicity was assessed in female C57BL\/6J mice, and possible interaction with mouse serum was also evaluated. Susceptibility testing revealed specific synergy with tetracyclines, with up to a 16-fold reduction in minimum inhibitory concentrations. Sequencing revealed that resistance to the RW01-minocycline combination involved mutations in the\n              <jats:italic>pmrB<\/jats:italic>\n              gene, affecting outer membrane lipopolysaccharide composition. This was further confirmed by the identification of cross-resistance to colistin in these mutants. RW01 reduced the mutant prevention concentration of minocycline from 64 to 8 mg\/L. RW01 was demonstrated to enhance membrane permeabilization and therefore minocycline uptake with statistical significance. Synthetic derivatives of RW01 showed a complete loss of activity, highlighting the importance of RW01\u2019s D-proline(NH2) residue. No acute or cumulative\n              <jats:italic>in vivo<\/jats:italic>\n              toxicity was observed in mice. These findings suggest that RW01 could revitalize obsolete antimicrobials and potentially expand therapeutic options against multidrug-resistant\n              <jats:italic>P. aeruginosa<\/jats:italic>\n              .\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1128\/aac.01459-24","type":"journal-article","created":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T14:01:42Z","timestamp":1734962502000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":3,"title":["<i>In vitro<\/i>\n            potentiation of tetracyclines in\n            <i>Pseudomonas aeruginosa<\/i>\n            by RW01, a new cyclic peptide"],"prefix":"10.1128","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3005-9981","authenticated-orcid":false,"given":"Natalia","family":"Roson-Calero","sequence":"first","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal)","place":["Barcelona, Spain"]},{"name":"Department of Basic Clinical Practice, School of Medicine, University of Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda A.","family":"Gomis Font","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III","place":["Madrid, Spain"]},{"name":"Department of Microbiology, Hospital Universitario Son Espases, Health Research Institute of the Balearic Islands (IdISBa)","place":["Palma de Mallorca, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"Ruiz-Soriano","sequence":"additional","affiliation":[{"name":"Laboratori de Qu\u00edmica Org\u00e0nica, Facultat de Farm\u00e0cia, Universitat de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Just-Baringo","sequence":"additional","affiliation":[{"name":"Laboratori de Qu\u00edmica Org\u00e0nica, Facultat de Farm\u00e0cia, Universitat de Barcelona","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Eugenia","family":"Pach\u00f3n-Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III","place":["Madrid, Spain"]},{"name":"Clinical Unit of Infectious Diseases, Microbiology and Parasitology, Institute of Biomedicine of Seville (IBiS), Virgen del Rocio University Hospital\/CSIC\/University of Seville","place":["Seville, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Pablo","family":"Salvador","sequence":"additional","affiliation":[{"name":"Nanobiotechnology for Diagnostics (Nb4D), Department of Chemical and Biomolecular Nanotechnology, Institute for Advanced Architecture of Catalonia (IQAC) of the Spanish Council for Scientific Research (CSIC)","place":["Barcelona, Spain"]},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER_BBN)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4064-1668","authenticated-orcid":true,"given":"M. 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