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The results revealed significant genetic diversity among the isolates, with each exhibiting a distinct genetic profile. A prevalence of sequence type ST235 was observed, characterizing it as a high-risk clone, and serotyping indicated a predominance of type O11, associated with chronic respiratory infections in cystic fibrosis (CF) patients. The phylogenetic analysis demonstrated genetic diversity among the isolates, with distinct clades and complex evolutionary relationships. Additionally, transposable elements such as Tn3 and IS6 were identified in all isolates, highlighting their importance in the mobility of antibiotic resistance genes. An analysis of antimicrobial resistance profiles revealed pan-drug resistance in all isolates, with a high prevalence of genes conferring resistance to \u03b2-lactams and aminoglycosides. Furthermore, additional analyses revealed mutations in regulatory networks and specific loci previously implicated in colistin resistance, such as pmrA, cprS, phoO, and others, suggesting a possible contribution to the observed resistant phenotype. This study has a strong impact because it not only reveals the genetic diversity and resistance mechanisms in P. aeruginosa but also identifies mutations in regulatory genes associated with colistin resistance.<\/jats:p>","DOI":"10.3390\/pathogens14040387","type":"journal-article","created":{"date-parts":[[2025,4,15]],"date-time":"2025-04-15T09:41:11Z","timestamp":1744710071000},"page":"387","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Mutational Analysis of Colistin-Resistant Pseudomonas aeruginosa Isolates: From Genomic Background to Antibiotic Resistance"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2326-6226","authenticated-orcid":false,"given":"Telma","family":"De Sousa","sequence":"first","affiliation":[{"name":"MicroART\u2014Antibiotic Resistance Team, Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Department of Genetics and Biotechnology, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Functional Genomics and Proteomics Unit, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Associated Laboratory for Green Chemistry, University NOVA of Lisbon, 1099-085 Caparica, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5581-6793","authenticated-orcid":false,"given":"Hsin-Yao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan"},{"name":"School of Medicine, National Tsing Hua University, Hsinchu 300, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting-Wei","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2077-6231","authenticated-orcid":false,"given":"Manuela","family":"Cani\u00e7a","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Antibiotic Resistance and Healthcare Associated Infections, Department of Infectious Diseases, National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"},{"name":"Centre for the Studies of Animal Science (CECA), Institute of Agrarian and Agri-Food Sciences and Technologies, University of Porto, 4099-002 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel J. N.","family":"Ramos","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Antibiotic Resistance and Healthcare Associated Infections, Department of Infectious Diseases, National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3648-8410","authenticated-orcid":false,"given":"Daniela","family":"Santos","sequence":"additional","affiliation":[{"name":"National Reference Laboratory of Antibiotic Resistance and Healthcare Associated Infections, Department of Infectious Diseases, National Institute of Health Dr. Ricardo Jorge, 1649-016 Lisbon, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catarina","family":"Silva","sequence":"additional","affiliation":[{"name":"MicroART\u2014Antibiotic Resistance Team, Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8857-4038","authenticated-orcid":false,"given":"S\u00f3nia","family":"Saraiva","sequence":"additional","affiliation":[{"name":"MicroART\u2014Antibiotic Resistance Team, Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"CECAV\u2014Veterinary and Animal Research Centre, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5881-976X","authenticated-orcid":false,"given":"Racha","family":"Beyrouthy","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, (UMR1071), Institute National de la Recherche Agronomique (USC-2018), Universit\u00e9 Clermont Auvergne, 63000 Clermont-Ferrand, France"},{"name":"Centre National de R\u00e9f\u00e9rence de la R\u00e9sistance aux Antibiotiques, Centre Hospitalier Universitaire, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Bonnet","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, (UMR1071), Institute National de la Recherche Agronomique (USC-2018), Universit\u00e9 Clermont Auvergne, 63000 Clermont-Ferrand, France"},{"name":"Centre National de R\u00e9f\u00e9rence de la R\u00e9sistance aux Antibiotiques, Centre Hospitalier Universitaire, 63000 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0478-2575","authenticated-orcid":false,"given":"Michel","family":"H\u00e9braud","sequence":"additional","affiliation":[{"name":"INRAE, Universit\u00e9 Clermont Auvergne, UMR Microbiologie Environnement Digestif Sant\u00e9 (MEDiS), 63122 Saint-Gen\u00e8s-Champanelle, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6365-0735","authenticated-orcid":false,"given":"Gilberto","family":"Igrejas","sequence":"additional","affiliation":[{"name":"Department of Genetics and Biotechnology, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Functional Genomics and Proteomics Unit, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Associated Laboratory for Green Chemistry, University NOVA of Lisbon, 1099-085 Caparica, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0925-689X","authenticated-orcid":false,"given":"Patr\u00edcia","family":"Poeta","sequence":"additional","affiliation":[{"name":"MicroART\u2014Antibiotic Resistance Team, Department of Veterinary Sciences, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Associated Laboratory for Green Chemistry, University NOVA of Lisbon, 1099-085 Caparica, Portugal"},{"name":"CECAV\u2014Veterinary and Animal Research Centre, University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"},{"name":"Veterinary and Animal Research Centre, Associate Laboratory for Animal and Veterinary Science (AL4AnimalS), University of Tr\u00e1s-os-Montes and Alto Douro, 5000-801 Vila Real, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.mib.2021.09.010","article-title":"Pseudomonas Aeruginosa: An Antibiotic Resilient Pathogen with Environmental Origin","volume":"64","author":"Laborda","year":"2021","journal-title":"Curr. 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