Multi-omics investigation reveals unique markers underpinning the success of Klebsiella pneumoniae over closely related species

Abstract

Background The Klebsiella pneumoniae (KP) species complex comprises KP as the predominant species, and four others including Klebsiella variicola (KV) and Klebsiella quasipneumoniae (KQ), all capable of causing clinical infections and often challenging to differentiate. The emergence of multidrug-resistant and hypervirulent KP strains has led to severe infections with limited treatment options, underscoring the need to understand the factors contributing to KP's prevalence. Methods This study compared globally disseminated KP lineages with less abundant KV and KQ strains across multiple omics levels to identify characteristics potentially explaining KP's success over closely related species. Results We identified 107 genes of the core genome in eight clinical KP strains from four different sequence types (STs). Transcriptome and proteome analyses in human urine-like medium revealed different regulatory patterns between KP and KV strains, with metabolic responses playing a pivotal role. A total of 193 genes specific to the investigated KP STs were identified, exhibiting differential expression at the transcriptomic and/or proteomic levels. Comparison of these regulated genes to over 6,000 publicly available Klebsiella genomes highlighted genes adaptively regulated or uniquely present in KP genomes. For example, a gene cluster for the cellobiose phosphotransferase system, previously linked to bacterial virulence and biofilm formation, was found exclusively in KP. Conclusion Our study underscores the metabolic flexibility of KP strains in response to specific environmental conditions, potentially crucial for their success as opportunistic pathogens. We identified markers enriched in KP STs, providing a foundation for future investigations and potential utilization in alternative treatment strategies to conventional antibiotics.