Wang Meng, Jin Longyang, Wang Ruobing, Wang Qi, Wang Shuyi, Wu Xingyu, Yao Chaoqun, Corander Jukka, Wang Hui
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China.
Department of Clinical Laboratory, Peking University People's Hospital, Beijing, China; Institute of Medical Technology, Peking University Health Science Center, Beijing, China.
Drug Resist Updat. 2025 Jul;81:101243. doi: 10.1016/j.drup.2025.101243. Epub 2025 Apr 8.
Hypervirulent and carbapenem-resistant pathogens posed a significant and growing threat to global public health. This study focused on the rapid spread of a hypervirulent carbapenem-resistant E. coli (hv-CREC) subclone and its genomic resembles with hypervirulent carbapenem-resistant K. pneumoniae (hv-CRKP), driven by recombination impacting both chromosomal and plasmid gene content.
A multicenter molecular epidemiological study was conducted on 653 CREC clinical isolates collected across China (2013-2022), integrated with public genomic data. Pangenome-wide and phylogeographical analyses were performed to uncover recombination events, define the epidemic clone, and trace its evolutionary history. Growth advantage and virulence were evaluated through competition assays and Galleria mellonella infection models.
Sequence types (ST) 167, ST410, ST617, and ST361 collectively accounted for 53.8 % (351/653) of the CREC isolates, with ST167 showing a sharp increase in prevalence after 2017. Among these, subclone named KpnK48 emerged as the primary driver of the increase in ST167 CREC prevalence. Traced to a European origin, KpnK48 rapidly expanded globally, particularly in China. The remarkable success of KpnK48 could plausibly be attributed to enhanced survival and virulence, driven by the acquisition of a ∼492 kb recombinant genomic region which mirrored the genomic architecture underlying the hv-CRKP ST11-K64 clone, reflecting a Klebsiella-like evolutionary path. Additionally, plasmid shift in KpnK48 clone from the prevalent NDM-IncX3 plasmid to Klebsiella-common NDM-IncF plasmid expanded its resistance spectrum and virulence gene repertoire, likely further amplifying its pathogenicity and success.
The KpnK48 subclone combined the features of hypervirulence and carbapenem resistance, bridging genomic traits of E. coli and K. pneumoniae, signifying a broader evolutionary trend with profound global health implications.
高毒力和耐碳青霉烯类病原体对全球公共卫生构成了重大且日益增长的威胁。本研究聚焦于一种高毒力耐碳青霉烯类大肠杆菌（hv-CREC）亚克隆的快速传播及其与高毒力耐碳青霉烯类肺炎克雷伯菌（hv-CRKP）的基因组相似性，这种相似性由影响染色体和质粒基因内容的重组所驱动。
对在中国收集的653株CREC临床分离株（2013 - 2022年）进行了多中心分子流行病学研究，并整合了公共基因组数据。进行了全基因组范围和系统地理学分析，以揭示重组事件、定义流行克隆并追溯其进化历史。通过竞争试验和大蜡螟感染模型评估生长优势和毒力。
序列类型（ST）167、ST410、ST617和ST361共占CREC分离株的53.8%（351/653），其中ST167在2017年后患病率急剧上升。其中，名为KpnK48的亚克隆成为ST167 CREC患病率增加的主要驱动因素。追溯到欧洲起源，KpnK48在全球迅速扩张，尤其是在中国。KpnK48的显著成功可能归因于其生存能力和毒力的增强，这是由获得一个约492 kb的重组基因组区域所驱动的，该区域反映了hv-CRKP ST11-K64克隆的基因组结构，反映了类似克雷伯菌的进化路径。此外，KpnK48克隆中的质粒从流行的NDM-IncX3质粒转变为克雷伯菌常见的NDM-IncF质粒，扩大了其耐药谱和毒力基因库，可能进一步增强了其致病性和成功传播。
KpnK48亚克隆兼具高毒力和耐碳青霉烯类的特征，弥合了大肠杆菌和肺炎克雷伯菌的基因组特征，标志着一种具有深远全球健康影响的更广泛进化趋势。
