Genome-Wide Association of ST, K-, and O-Locus Diversity with Virulence in Indian Klebsiella pneumoniae via Targeted Phenotypic Validation
摘要
Klebsiella pneumoniae is an opportunistic pathogen that causes pneumonia, bacteremia, and urinary tract infections, primarily in healthcare settings. The capsule, lipopolysaccharide, siderophores, and fimbriae are all virulence factors that contribute to its pathogenicity. We leveraged publicly accessible sequence data to outline the distribution of virulence loci; thereafter, nine representative isolates with varied ST-K-O profiles and rmpA/A2 markers underwent targeted phenotypic testing to connect genomic predictions with functional pathogenicity. We conducted an in-depth analysis of the genetic (n = 351) and phenotypic (n = 9) characteristics of Indian isolates, combining 29 of our clinical samples with an extensive dataset from the BV-BRC database. Using modern genomic techniques, we generated the “blueprints” {sequence types and surface antigens (ST-K locus-O locus)} and then validated these results in the lab by looking at different phenotypic traits linked to virulence to see how well the bacteria could survive the immune response. The findings indicated an exceptionally varied environment with 93 distinct sequence types. ST231 and ST14 are the predominant strains in India, frequently associated with the K51 and K64 capsules. Although certain “classic” hypervirulent strains such as ST23 exhibited their vast collection of genes, we observed an unanticipated phenomenon: conventional markers did not consistently align with the actual findings. For example, isolate M58 exhibited remarkable viscosity and mucoid characteristics despite possessing a small capsule, but other isolates with “threatening” genetic profiles were easily eliminated by human serum. Ultimately, our research reveals that virulence is far from a fixed biological constant. Instead, it is a dynamic outcome of specific genomic architectures, proving that no single marker can perfectly predict how dangerous a strain is. This complexity highlights why we must move toward continuous, integrated genomic monitoring to stay one step ahead of these evolving, drug-resistant threats in India.