Epidemiological and functional insights into iroBCDN loss in ST11 carbapenem-resistant hypervirulent Klebsiella pneumoniae

作者：Jia-wei Ding, M. Xu, Mengying Zhang, Jiyong Chang, Zhekai Hu, Yu Yan, Yao Yao, Shen Ni, Wenlin Tai, Lei Feng · 发表于：Microbiology Spectrum · 年份：2025 · DOI：10.1128/spectrum.02479-25 · 被引用次数：1 · 研究领域：Antibiotic Resistance in Bacteria、Bacterial Genetics and Biotechnology、Antimicrobial agents and applications

ABSTRACT Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP) has emerged as a major public health threat due to its high virulence, multidrug resistance, and increasing global prevalence. However, the molecular characteristics and adaptive mechanisms underlying the CR-hvKP pathogenesis remain poorly understood. In this study, we collected 217 CRKP isolates from a tertiary hospital and identified 46 as CR-hvKP. Genomic analysis revealed that the majority of CR-hvKP strains belonged to ST11-KL64 (48.7%, 20/46) and ST11-KL25 (46.3%, 19/46), followed by ST11-KL47 (4.8%, 2/46). Interestingly, while iroBCDN was present in various sequence types, it was found in ST11 strains only with the KL47 capsule type, which showed high virulence in Galleria mellonella models. To investigate the biological role of iroBCDN , we constructed an iroBCDN deletion mutant and a complemented strain in an ST11-KL47 background. The lactate dehydrogenase cytotoxicity assays and G. mellonella infection models revealed no significant difference in virulence among the wild-type, knockout, and complemented strains. Remarkably, phenotypic assays showed that the iroBCDN deletion mutant exhibited enhanced growth fitness, competitive advantage, oxidative stress resistance, and survival in human whole blood. Transcriptomic analysis revealed that iroBCDN deletion led to the upregulation of genes involved in oxidative stress response, capsule biosynthesis, and energy metabolism, while genes related to...