Genomic analysis and antimicrobial resistance profiling of Klebsiella pneumoniae clinical isolates from urinary tract infections in India: prevalence of class A β-lactamase with molecular docking and simulation insights

Urinary tract infections are a major global health concern, with Klebsiella pneumoniae emerging as a prominent multidrug-resistant uropathogen. The increasing prevalence of extended-spectrum β-lactamase-producing strains has reduced the effectiveness of β-lactam antibiotics. In this study, 87 clinical K. pneumoniae isolates from India were analysed using whole-genome sequencing, MLST and antimicrobial resistance profiling. β-Lactam resistance was the dominant phenotype, with blaSHV and blaCTX-M identified as the most prevalent class A β-lactamase genes. Molecular docking and 100 ns molecular dynamics simulations were conducted to examine enzyme-antibiotic interactions. Meropenem exhibited the lowest binding affinity with both proteins (-2.695 kcal mol-1 for blaSHV and -1.849 kcal mol-1 for blaCTX-M), forming unstable complexes, particularly with blaCTX-M. These findings highlight the growing challenge of β-lactam resistance and emphasize the need for genomic surveillance and alternative therapeutic strategies against multidrug-resistant K. pneumoniae.