{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T12:04:11Z","timestamp":1784721851612,"version":"3.55.0"},"reference-count":67,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Lung infections represent a major cause of morbidity and mortality in patients with cystic fibrosis (CF) and are predominantly associated with chronic infection by Pseudomonas aeruginosa. The clinical management of CF lung disease is increasingly compromised by the emergence of multidrug-resistant strains, biofilm formation, and the expression of multiple virulence determinants. Antimicrobial peptides (AMPs), evolutionarily conserved effectors of innate immunity, have emerged as promising therapeutic candidates due to their ability to exert both bactericidal and anti-virulence activities. In this study, we investigated the antimicrobial and mechanistic effects of Ranalexin-1G, an AMP derived from the skin secretion of Rana grylio, against P. aeruginosa, for which its antibacterial activity has not previously been reported in the literature. Methods: Antibacterial activity was determined against the reference strain and three clinical isolates of P. aeruginosa by broth microdilution assays, time-kill kinetics and anti-biofilm assays, while peptide-mediated modulation of virulence was evaluated through transcriptional analysis of key virulence-associated genes by RT-PCR. The impact of Ranalexin-1G on host\u2013pathogen interactions was further assessed using bacterial invasion assays in human bronchial epithelial cells (BEAS-2B). Results: Ranalexin-1G exerted a rapid bactericidal effect within 6 h at non-cytotoxic concentrations and displayed modest anti-biofilm effects, with greater efficacy in inhibiting biofilm formation. Mechanistically, peptide treatment resulted in a reduction in the expression of selected genes involved in biofilm formation and virulence, including those associated with alginate biosynthesis and type III secretion system-mediated cytotoxicity. Consistently, Ranalexin-1G markedly impaired bacterial invasion of epithelial cells, indicating interference with early host\u2013pathogen interaction processes. Notably, the peptide displayed robust antimicrobial activity against multidrug-resistant P. aeruginosa clinical isolates from CF patients. Conclusions: Collectively, these findings suggest that Ranalexin-1G acts through a dual mechanism involving direct bactericidal activity and modulation of selected virulence pathways, supporting further investigation of its potential as an anti-virulence and host-directed approach for the treatment of chronic P. aeruginosa infections in cystic fibrosis.<\/jats:p>","DOI":"10.3390\/antibiotics15070711","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:48:28Z","timestamp":1784717308000},"page":"711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ranalexin-1G: A Promising Antimicrobial Peptide Targeting Virulence and Host\u2013Pathogen Interactions in Pseudomonas aeruginosa In Vitro Models"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1483-7054","authenticated-orcid":false,"given":"Marina","family":"Acunzo","sequence":"first","affiliation":[{"name":"Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7991-8700","authenticated-orcid":false,"given":"Carla","family":"Zannella","sequence":"additional","affiliation":[{"name":"Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"},{"name":"UOC Virology and Microbiology, University Hospital \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9923-3194","authenticated-orcid":false,"given":"Rosa","family":"Giugliano","sequence":"additional","affiliation":[{"name":"Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7849-9484","authenticated-orcid":false,"given":"Laura","family":"Di Clemente","sequence":"additional","affiliation":[{"name":"Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6430-9343","authenticated-orcid":false,"given":"Carla","family":"Capasso","sequence":"additional","affiliation":[{"name":"Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1648-4519","authenticated-orcid":false,"given":"Annalisa","family":"Chianese","sequence":"additional","affiliation":[{"name":"Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"},{"name":"Department of Life Sciences, Health and Health Professions, Link Campus University, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Andriolo","sequence":"additional","affiliation":[{"name":"Clinical Pathology Unit, Sant\u2019 Elia Hospital, 93100 Caltanissetta, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Donadio","sequence":"additional","affiliation":[{"name":"Institute of Applied Sciences and Intelligent Systems (ISASI), National Research Council (CNR), Naples Cryo-Electron Microscopy Laboratory (M6.1 EYE LAB), Via Pietro Castellino 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5347-247X","authenticated-orcid":false,"given":"Emanuela","family":"Esposito","sequence":"additional","affiliation":[{"name":"Institute of Applied Sciences and Intelligent Systems (ISASI), National Research Council (CNR), Naples Cryo-Electron Microscopy Laboratory (M6.1 EYE LAB), Via Pietro Castellino 111, 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6789-7057","authenticated-orcid":false,"given":"Alessandra","family":"Monti","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2952-6658","authenticated-orcid":false,"given":"Nunzianna","family":"Doti","sequence":"additional","affiliation":[{"name":"Institute of Biostructures and Bioimaging (IBB), National Research Council (CNR), 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa Maria Assunta","family":"Fasciana","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Giammanco","sequence":"additional","affiliation":[{"name":"Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90127 Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1576-6290","authenticated-orcid":false,"given":"Massimiliano","family":"Galdiero","sequence":"additional","affiliation":[{"name":"Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"},{"name":"UOC Virology and Microbiology, University Hospital \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0395-7962","authenticated-orcid":false,"given":"Anna De","family":"Filippis","sequence":"additional","affiliation":[{"name":"Department of Woman, Child and General and Specialized Surgery, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"},{"name":"UOC Virology and Microbiology, University Hospital \u201cLuigi Vanvitelli\u201d, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1001\/jama.2023.8120","article-title":"Cystic Fibrosis: A Review","volume":"329","author":"Ong","year":"2023","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.biocel.2014.02.023","article-title":"Genetics of cystic fibrosis: CFTR mutation classifications toward genotype-based CF therapies","volume":"52","author":"Fanen","year":"2014","journal-title":"Int. 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