Genomic and transcriptomic analysis revealed new insights into the influence of key T6SS genes hcp and vgrG on drug resistance and interbacterial competition in Klebsiella pneumoniae

Type VI secretion systems (T6SSs) act as a molecular weapon in interbacterial competition and play an important role in cell-cell interactions. Different species of bacteria use their T6SSs to perform a variety of functions according to ecological niche. Therefore, it is necessary to better understand the T6SS potential of Klebsiella pneumoniae (K. pneumoniae), a common clinical opportunistic pathogen. Here, we conducted a genomic analysis on the evolution, T6SS, virulence and antimicrobial resistance of 65 K. pneumoniae in patients with different infections. And we combined transcriptome analysis after knockout of key gene in T6SS of this species. Results showed that genes encoding a T6SS were present in all K. pneumoniae in this study, and there was no correlation was found between T6SS cluster and carbapenem resistance and virulence genes. Differentially expressed genes (DEGs) including 1298 co-upregulated and 1714 co-downregulated were identified after hcp or vgrG deletion. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways analysis have demonstrated common changes in quorum sensing, propionate metabolism and other pathways. And we found that the deletion of hcp or vgrG genes up-regulated of beta-lactam (blaKPC-2) and other resistance genes. Interbacterial competition experiments showed that hcp and vgrG are essential genes for competitive ability of ST11 K. pneumoniae. Taken together, the entire study provides further insight into the investigation of T6SS in K. pneumoniae through genomic and transcriptomic analysis. ImportanceGram-negative bacteria use T6SS to deliver toxin effectors to interact with neighboring cells for niche advantage. K. pneumoniae is an opportunistic nosocomial pathogen that often carriers multiple cope T6SSs, but the function of its T6SS has not yet elucidated. Here, we performed a genomic analysis of 65 clinical K. pneumoniae strains, in order to explore the relationship between T6SS and virulence and resistance genes. We also study the repertoire after knockout of key gene in T6SS of this species by transcriptomics. It was suggested that T6SS is associated with drug resistance, and its key genes hcp and vgrG are critical for the interspecies competition of K. pneumoniae.