@article{4cea05f9ac0b46a3b95abbc1899c3af6,
title = "A point mutation in recC associated with subclonal replacement of carbapenem-resistant Klebsiella pneumoniae ST11 in China",
abstract = "Adaptation to selective pressures is crucial for clinically important pathogens to establish epidemics, but the underlying evolutionary drivers remain poorly understood. The current epidemic of carbapenem-resistant Klebsiella pneumoniae (CRKP) poses a significant threat to public health. In this study we analyzed the genome sequences of 794 CRKP bloodstream isolates collected in 40 hospitals in China between 2014 and 2019. We uncovered a subclonal replacement in the predominant clone ST11, where the previously prevalent subclone OL101:KL47 was replaced by O2v1:KL64 over time in a stepwise manner. O2v1:KL64 carried a higher load of mobile genetic elements, and a point mutation exclusively detected in the recC of O2v1:KL64 significantly promotes recombination proficiency. The epidemic success of O2v1:KL64 was further associated with a hypervirulent sublineage with enhanced resistance to phagocytosis, sulfamethoxazole-trimethoprim, and tetracycline. The phenotypic alterations were linked to the overrepresentation of hypervirulence determinants and antibiotic genes conferred by the acquisition of an rmpA-positive pLVPK-like virulence plasmid and an IncFII-type multidrug-resistant plasmid, respectively. The dissemination of the sublineage was further promoted by more frequent inter-hospital transmission. The results collectively demonstrate that the expansion of O2v1:KL64 is correlated to a repertoire of genomic alterations convergent in a subpopulation with evolutionary advantages.",
author = "Kai Zhou and Xue, {Chun Xu} and Tingting Xu and Ping Shen and Sha Wei and Wyres, {Kelly L.} and Lam, {Margaret M.C.} and Jinquan Liu and Haoyun Lin and Yunbo Chen and Holt, {Kathryn E.} and Yunbo Chen and Hui Ding and Yongyun Liu and Haifeng Mao and Ying Huang and Zhenghai Yang and Yuanyuan Dai and Guolin Liao and Lisha Zhu and Liping Zhang and Yanhong Li and Hongyun Xu and Junmin Cao and Baohua Zhang and Liang Guo and Haixin Dong and Shuyan Hu and Sijin Man and Lu Wang and Zhixiang Liao and Rong Xu and Dan Liu and Yan Jin and Yizheng Zhou and Yiqun Liao and Fenghong Chen and Beiqing Gu and Jiliang Wang and Jinhua Liang and Lin Zheng and Aiyun Li and Jilu Shen and Yinqiao Dong and Lixia Zhang and Hongxia Hu and Bo Quan and Wencheng Zhu and Kunpeng Liang and Qiang Liu and Shifu Wang and Xiaoping Yan and Jiangbang Kang and Xiusan Xia and Lan Ma and Li Sun and Liang Luan and Jianzhong Wang and Haoyun Lin and Zhuo Li and Dengyan Qiao and Lin Zhang and Chuandan Wan and Xiaoyan Qi and Fei Du and {the BRICS Working Group} and Yonghong Xiao",
note = "Funding Information: We thank Jingjie Song and Yang Liu for their technical support of bioinformatics. We also thank Jinru Ji and Chaoqun Ying for preparing the metadata of the collection. This work was funded by the National Key R&D Program of China under award numbers 2021YFC2300300 (to K.Z. and Y.X.) and 2022YFE0103200 (to K.Z.), the National Natural Science Foundation of China under award numbers 81902030 (to T.X.), 81971984 (to Y.X.), and 82172330 (to K.Z.), China Postdoctoral Science Foundation under award number 2022M712187 (to C.-X.X.), Shenzhen Basic Research Key projects under award number JCYJ20200109144220704 (to K.Z.), Shenzhen Basic Research projects under award number JCYJ20190807144409307 (to K.Z.), the Fundamental Research Funds for the Central Universities under award number 2022ZFJH003 (to Y.X.), and Research Project of Jinan Microecological Biomedicine Shandong Laboratory under award number JNL-2022027C (to Y.X.). Publisher Copyright: {\textcopyright} 2023, The Author(s).",
year = "2023",
month = apr,
day = "28",
doi = "10.1038/s41467-023-38061-z",
language = "English",
volume = "14",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
number = "1",
}
