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In this study, an integrative computational target\u2010discovery and drug\u2010repurposing framework was applied to six clinically relevant\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    strains. Comparative genomic analysis identified 3012 conserved genes, which were subsequently filtered to nine essential, non\u2010host homologous proteins. Among these, three conserved cytoplasmic proteins (\n                    <jats:italic>accD<\/jats:italic>\n                    ,\n                    <jats:italic>cpxR<\/jats:italic>\n                    , and\n                    <jats:italic>mraZ<\/jats:italic>\n                    ) were prioritized for functional analysis, with acetyl\u2010CoA carboxylase subunit beta (\n                    <jats:italic>accD<\/jats:italic>\n                    ) emerging as the most promising therapeutic target based on sequence conservation, predicted essentiality, subcellular localization, and pathway association. Structural assessment supported the reliability of the predicted\n                    <jats:italic>accD<\/jats:italic>\n                    model, whereas consensus binding\u2010site analysis identified key residues suitable for ligand interaction. Virtual screening of FDA\u2010approved drugs followed by molecular docking identified several compounds with favorable binding profiles toward\n                    <jats:italic>accD<\/jats:italic>\n                    . Subsequent molecular dynamics simulations, including root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), hydrogen\u2010bond occupancy, principal component analysis (PCA), and PCA\u2010based free energy landscape (FEL) analyses, consistently identified tenapanor, micafungin, deferoxamine, and cobicistat as the most stable protein\u2010ligand complexes, with tenapanor exhibiting the most favorable overall structural and thermodynamic stability profile. These findings identify\n                    <jats:italic>accD<\/jats:italic>\n                    as a promising therapeutic target in MDR\n                    <jats:italic>K. pneumoniae<\/jats:italic>\n                    and suggest several FDA\u2010approved compounds as potential candidates for drug repurposing. Although experimental validation is needed to confirm their biological activity and therapeutic potential, this study demonstrates the potential of integrating comparative genomics with molecular dynamics analyses to support antimicrobial target identification and drug repurposing against MDR bacterial pathogens.\n                  <\/jats:p>","DOI":"10.1155\/ijm\/1460586","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:34:32Z","timestamp":1788777272000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative and Subtractive Genomics Analysis of Multidrug\u2010Resistant\n                    <i>Klebsiella pneumoniae<\/i>\n                    Strains for Novel Target Identification and Drug Repurposing Strategies"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-1629-1170","authenticated-orcid":false,"given":"Manasi","family":"Bora","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8316-1008","authenticated-orcid":false,"given":"Prokriti","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4834-2654","authenticated-orcid":false,"given":"Sanchaita","family":"Rajkhowa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-9675-0143","authenticated-orcid":false,"given":"Harshita","family":"Sonar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8676-0204","authenticated-orcid":false,"given":"Borakha Bura","family":"Gohain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5643-9202","authenticated-orcid":false,"given":"Magdi E. 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