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It shows rapid evolution of multidrug resistance (MDR). Phenotype-based diagnostics often fail to detect silent resistance determinants and early adaptive changes. This study integrates phenotypic profiling with whole-genome sequencing (WGS) to examine resistance architecture in clinical isolates from eastern India.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      From 1295 culture-positive\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      specimens collected at a tertiary care hospital in eastern India. Using predefined criteria, representative MDR and non-MDR isolates were selected, including distinct resistance phenotypes, specimen-source diversity, and hospital and community-acquired settings; multivariate analysis of resistance profiles illustrated phenotypic diversity. Antimicrobial susceptibility assessed using VITEK-2 and Kirby-Bauer disk diffusion, species identity confirmed by 16\u00a0S rRNA sequencing, and genomic analysis processed through a reference-guided workflow. Antimicrobial Resistance (AMR) determinants were identified through CARD, and phylogenetic tree constructed from 454 publicly available\n                      <jats:italic>P. aeruginosa<\/jats:italic>\n                      genomes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>MDR exhibited greater sequence divergence relative to PA14 (~\u200969,000 variants) than the non-MDR isolate (~\u200958,700 variants), with &gt;\u200992% coverage at \u2265\u200930X depth. Strong genotype-phenotype concordance observed in MDR isolates across five antibiotic classes, associated with \u03b2-lactamase variants (PDC-67, OXA-396) and regulatory adaptations (ArmR, cprS). The non-MDR isolate harboured gyrA (T83I) resistance-associated mutations, PDC-1, and OXA-847 without phenotypic expression, indicating silent resistome. Phylogenetically, MDR isolates clustered tightly within the phylogeny, while the non-MDR isolate formed a distinct lineage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Observed genomic differences align with adaptation under antimicrobial selection, though confirmation requires larger collections. The non-MDR isolate retained a silent resistome. Findings highlight limitations of phenotype-only diagnostics, support genomic data integration, and emphasize transcriptomics for hidden resistance expression and regulatory dynamics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10123-026-00892-3","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:29:46Z","timestamp":1789172986000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative genomics reveals genotype-phenotype concordance and cryptic resistomes in clinical Pseudomonas aeruginosa"],"prefix":"10.1007","author":[{"given":"Sweta Padma","family":"Routray","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1853-4874","authenticated-orcid":false,"given":"Tripti","family":"Swarnkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0571-6940","authenticated-orcid":false,"given":"Enketeswara","family":"Subudhi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajashree","family":"Panigrahy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,12]]},"reference":[{"key":"892_CR1","doi-asserted-by":"publisher","unstructured":"Elfadadny A, Ragab RF, AlHarbi M, Badshah F, Ib\u00e1\u00f1ez-Arancibia E, Farag A et al (2024) Antimicrobial resistance of Pseudomonas aeruginosa: navigating clinical impacts, current resistance trends, and innovations in breaking therapies. 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Mol Genet Genomics 299. https:\/\/doi.org\/10.1007\/s00438-024-02122-9","DOI":"10.1007\/s00438-024-02122-9"}],"container-title":["International Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10123-026-00892-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s10123-026-00892-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s10123-026-00892-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:29:48Z","timestamp":1789172988000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s10123-026-00892-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,12]]},"references-count":58,"alternative-id":["892"],"URL":"https:\/\/doi.org\/10.1007\/s10123-026-00892-3","relation":{},"ISSN":["1618-1905"],"issn-type":[{"value":"1618-1905","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,12]]},"assertion":[{"value":"15 June 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 August 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 September 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Ethical approval was obtained from the Institutional Ethics Committee of IMS & SUM Hospital, Siksha \u2018O\u2019 Anusandhan deemed to be University (Ref. no\/IEC\/IMS.SH\/SOA\/2022\/401). This study involved laboratory- based analysis of de-identified bacterial isolates obtained following routine clinical diagnosis. NO human participants were directly involved, and no identifiable patient data were used. The requirement for informed consent to participate was waived by the Institutional Ethics Committee due to the use of de-identified clinical isolates.","order":1,"name":"Ethics","label":"Ethical approval and consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","label":"Competing interest","group":{"name":"EthicsHeading","label":"Declarations"}}]}}