Genomic insights into Klebsiella pneumoniae: Virulence, resistance, and transmission in South and Southeast Asia

<h4>Background</h4>Klebsiella pneumoniae has long posed a significant challenge in clinical settings worldwide, particularly due to its carbapenemase production and multidrug-resistant (MDR) characteristics. While extensive genomic studies of K. pneumoniae have been conducted globally, research in Asia, particularly South Asia, remains limited.<h4>Objectives</h4>This study aims to address and compare the genomic characteristics of K. pneumoniae isolates from South Asia and Southeast Asia, including virulence, antimicrobial resistance (AMR), plasmids, and mobile genetic elements (MGE) profiles, as well as potential transmission dynamics.<h4>Methods</h4>A total of 463 K. pneumoniae genomes were included from collected samples and public databases. All genomes underwent comprehensive analysis, including pan-genome profiling, multi-locus sequence typing (MLST), annotation of virulence factors, AMR genes, plasmids, and MGEs, as well as SNP distance-based analysis to infer transmission dynamics, using established bioinformatic tools.<h4>Results</h4>K. pneumoniae isolates exhibited diverse virulence determinants. Hypervirulent isolates were primarily associated with ST23 and ST86, and commonly harbour aerobactin, salmochelin, and rmpA. The majority of isolates were predicted to be MDR, with those from Southeast Asia showing a higher relative abundance of AMR genes associated with the antibiotic classes examined in this study. Among all isolates, the predominant carbapenemase-associated gene was bla_NDM-1. Col440I_1 was the most prevalent plasmid replicon, although it did not co-occur with any AMR genes. Association between the IncFII_1_pKP9 plasmid replicon and resistance genes sul-5, bla_CTX-M, and bla_TEM was found. ISSen9 was the dominant MGE, frequently co-occurring with the plasmid replicons IncFIB(K)_1_Kpn3 and IncFII_1_pKP91. Transmission analysis indicated that the highest isolate similarity occurred within MLST and country. However, clustering based on plasmid replicon profiles revealed that some clusters comprised isolates from multiple countries.<h4>Conclusion</h4>This study provides a comprehensive analysis of the genomic characteristics and transmission patterns of K. pneumoniae in South and Southeast Asia, contributing to our understanding of its virulence and resistance mechanisms. These findings further suggest that plasmid replicons may play a critical role in shaping transmission dynamics and provide valuable insights to inform future AMR surveillance and control strategies.