{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:33:25Z","timestamp":1787027605887,"version":"build-2736575974"},"reference-count":80,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2024,12,1]],"date-time":"2024-12-01T00:00:00Z","timestamp":1733011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","award":["PI20\/0076"],"award-info":[{"award-number":["PI20\/0076"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Acinetobacter baumannii is a globally emerging pathogen with widespread antimicrobial resistance driven by multiple mechanisms, such as altered expression of efflux pumps like AdeABC, placing it as a priority for research. Driven by the lack of new treatments, alternative approaches are being explored to combat its infections, among which efficacy-enhancing adjuvants can be found. This study presents and characterizes MV6, a synthetic cyclic peptide that boosts aminoglycoside efficacy. Methods: MV6\u2019s activity was assessed through antimicrobial susceptibility testing in combination with different antibiotic classes against A. baumannii strains characterized by PCR and RT-qPCR. PA\u03b2N served as a reference efflux pump inhibitor. Synergy was evaluated using checkerboard assays, and spontaneous mutants were generated with netilmicin with\/without MV6 (100 mg\/L). Whole-genome sequencing and variant calling analysis were then performed. Results: MV6 presented low antimicrobial activity in A. baumannii with MICs higher than 2048 mg\/L. MV6 showed a better boosting effect for aminoglycosides, especially netilmicin, exceeding that of PA\u03b2N. Checkerboard assays confirmed a strong synergy between netilmicin and MV6, and a significant correlation was found between netilmicin MIC and adeB overexpression, which was mitigated by the presence of MV6. MV6 reduced, by 16-fold, the mutant prevention concentration of netilmicin. Mutations in a TetR-family regulator and ABC-binding proteins were found in both groups, suggesting a direct or indirect implication of these proteins in the resistance acquisition process. Conclusions: MV6 lacks intrinsic antimicrobial activity, minimizing selective pressure, yet enhances netilmicin\u2019s effectiveness except for strain 210, which lacks the AdeABC efflux pump. Resistant mutants indicate specific aminoglycoside resistance mechanisms involving efflux pump mutations, suggesting synergistic interactions. Further research, including transcriptomic analysis, is essential to elucidate MV6\u2019s role in enhancing netilmicin efficacy and its resistance mechanisms.<\/jats:p>","DOI":"10.3390\/antibiotics13121147","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T05:43:43Z","timestamp":1733118223000},"page":"1147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Cyclic Peptide MV6, an Aminoglycoside Efficacy Enhancer Against Acinetobacter baumannii"],"prefix":"10.3390","volume":"13","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), 08036 Barcelona, Spain"},{"name":"Department of Basic Clinical Practice, School of Medicine, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8353-5818","authenticated-orcid":false,"given":"Jimmy","family":"Lucas","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6042-5674","authenticated-orcid":false,"given":"Mar\u00eda A.","family":"Gomis-Font","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Microbiology, Hospital Universitario Son Espases, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7083-7960","authenticated-orcid":false,"given":"Roger","family":"de Pedro-Jov\u00e9","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9327-1894","authenticated-orcid":false,"given":"Antonio","family":"Oliver","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Microbiology, Hospital Universitario Son Espases, Health Research Institute of the Balearic Islands (IdISBa), 07120 Palma de Mallorca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8589-2519","authenticated-orcid":false,"given":"Clara","family":"Ballest\u00e9-Delpierre","sequence":"additional","affiliation":[{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Clinical Microbiology, Biomedical Diagnostic Center, Hospital Clinic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8025-3926","authenticated-orcid":false,"given":"Jordi","family":"Vila","sequence":"additional","affiliation":[{"name":"Barcelona Institute for Global Health (ISGlobal), 08036 Barcelona, Spain"},{"name":"Department of Basic Clinical Practice, School of Medicine, University of Barcelona, 08036 Barcelona, Spain"},{"name":"CIBER de Enfermedades Infecciosas (CIBERINFEC), Instituto Salud Carlos III, 28029 Madrid, Spain"},{"name":"Department of Clinical Microbiology, Biomedical Diagnostic Center, Hospital Clinic, 08036 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1128\/CMR.00058-07","article-title":"Acinetobacter baumannii: Emergence of a Successful Pathogen","volume":"21","author":"Peleg","year":"2008","journal-title":"Clin. 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