Abstract
Klebsiella pneumoniae poses a significant global health threat due to its increasing prevalence of multidrug resistance (MDR) and hypervirulence. Understanding the genetic determinants underlying these phenotypes is crucial for effective surveillance and treatment strategies. This study employed a comparative pan-genomic approach to analyze 200 clinical isolates of K. pneumoniae collected from diverse geographical regions. Whole-genome sequencing data were used to construct the pan-genome, identifying core, accessory, and unique gene sets. We systematically identified and characterized virulence factors (VFs) using the Virulence Factor Database (VFDB) and antimicrobial resistance genes (ARGs) using the Comprehensive Antibiotic Resistance Database (CARD). Our analysis revealed an open pan-genome, indicative of extensive genetic diversity and horizontal gene transfer. We observed a high prevalence of specific VFs, such as those associated with siderophore production (e.g., iroB, iucA) and capsule synthesis (e.g., wzi alleles), alongside a diverse array of ARGs, including extended-spectrum β-lactamases (ESBLs) and carbapenemases (e.g., blaKPC, blaNDM). Critically, we identified the co-occurrence of multiple VFs and ARGs within specific clonal lineages, particularly ST258 and ST11, highlighting the emergence of highly concerning hypervirulent-MDR strains. These findings underscore the dynamic genomic landscape of K. pneumoniae and provide valuable insights into the genetic mechanisms driving its pathogenicity and antimicrobial resistance, paving the way for targeted diagnostic and therapeutic interventions.
