Adaptive evolution of carbapenem- resistant hypervirulent Klebsiella pneumoniae in the urinary tract of a single patient

• 成果类型: Article
• 署名作者: Song, Shikai; Yang, Shixin; Zheng, Ruicheng; Yin, Dandan; Cao, Yue; Wang, Yao; Qiao, Lu; Bai, Rina; Wang, Shuge; Yin, Wenjuan; Dong, Yanjun; Bai, Li; Yang, Hui; Shen, Jianzhong; Wu, Congming; Hu, Fupin; Wang, Yang
• 署名单位: China Agricultural University; Shandong Academy of Agricultural Sciences; Fudan University; Hebei University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13672
• DOI: 10.1073/pnas.2400446121
• 发表日期: 2024-08-27
• 关键词: within-host evolution; molecular epidemiology; staphylococcus-aureus; low virulence; PREVALENCE; CHINA; hypermucoviscosity; Mutation; rmpa

摘要

is a growing concern due to its high mortality and limited treatment options. Although hypermucoviscosity is crucial for CR- hvKp infection, the role of changes in bacterial mucoviscosity in the host colonization and persistence of CR- hvKp is not clearly defined. Herein, we observed a phenotypic switch of CR- hvKp from a hypermucoviscous to a hypomucoviscous state in a patient with scrotal abscess and urinary tract infection (UTI). This switch was attributed to decreased expression of rmpADC, the regulator of mucoid phenotype, caused by deletion of the upstream insertion sequence ISKpn26. Postswitching, the hypomucoid variant showed a 9.0- fold decrease in mice sepsis mortality, a >170.0- fold reduction in the ability to evade macrophage phagocytosis in vitro, and an 11.2- to 40.9- fold drop in growth rate in normal mouse serum. Conversely, it exhibited an increased residence time in the mouse urinary tract (21 vs. 6 d), as well as a 216.4- fold boost in adhesion to bladder epithelial cells and a 48.7% enhancement primarily associated with defective or low expression of rmpADC or capsule synthesis