肺炎克雷伯菌
微生物学
泌尿系统
碳青霉烯
克雷伯菌
克雷伯菌感染
生物
病毒学
革兰氏阴性细菌感染
医学
大肠杆菌
抗生素
内科学
基因
遗传学
作者
Shikai Song,Shixin Yang,Zheng Ruicheng,Dandan Yin,Yue Cao,Yao Wang,Lu Qiao,Rina Bai,Sheng Wang,Wenjuan Yin,Yanjun Dong,Li Bai,Hui Yang,Jianzhong Shen,Congming Wu,Fupin Hu,Yang Wang
标识
DOI:10.1073/pnas.2400446121
摘要
The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) 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 IS Kpn26 . 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 in biofilm production. Notably, the CR-hvKp mucoid switch was reproduced in an antibiotic-free mouse UTI model. The in vivo generation of hypomucoid variants was primarily associated with defective or low expression of rmpADC or capsule synthesis gene wcaJ , mediated by IS Kpn26 insertion/deletion or base-pair insertion. The spontaneous hypomucoid variants also outcompeted hypermucoid bacteria in the mouse urinary tract. Collectively, the IS Kpn26 -associated mucoid switch in CR-hvKp signifies the antibiotic-independent host adaptive evolution, providing insights into the role of mucoid switch in the persistence of CR-hvKp.
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