Insertion sequences accelerate genomic convergence of multidrug resistance and hypervirulence in Klebsiella pneumoniae via capsular phase variation

作者：Dawei Wei, Yuqin Song, Yi Li, Gang Zhang, Qi Chen, Linhuan Wu, Jiangqing Huang, Xueru Tian, Chao Wang, Jie Feng · 发表于：Genome Medicine · 年份：2025 · DOI：10.1186/s13073-025-01474-0 · 被引用次数：24 · 研究领域：Antibiotic Resistance in Bacteria、Bacterial Genetics and Biotechnology、Escherichia coli research studies

BACKGROUND: The convergence of resistance and hypervirulence in Klebsiella pneumoniae represents a significant public health threat, driven by the horizontal transfer of plasmids. Understanding factors affecting plasmid transfer efficiency is essential to elucidate mechanisms behind emergence of these formidable pathogens. METHODS: Hypermucoviscous K. pneumoniae strains were serially passaged in LB medium to investigate capsule-deficient phenotypes. Capsule-deficient mutants were analyzed using genetic sequencing to identify the types and insertion sites of insertion sequences (IS). Bioinformatics and statistical analyses based on the NCBI and National Microbiology Data Center (NMDC) database were used to map the origins and locations of IS elements. Conjugation assays were performed to assess plasmid transfer efficiency between encapsulated and capsule-deficient strains. A murine intestinal colonization model was employed to evaluate virulence levels and IS excision-mediated capsule restoration. RESULTS: -bearing IncX3 plasmid with IS5 and ISKox3 elements. These IS elements are capable of inserting into capsular polysaccharide synthesis genes, causing a notably high frequency of capsule loss in vitro. The IS-mediated capsular phase variation, whether occurring in the donor or recipient strain, significantly increased the conjugation frequency of both the resistance plasmid and the virulence plasmid. Additionally, capsular phase variation enhanced bacterial adaptability in vi...