A point mutation in recC associated with subclonal replacement of carbapenem-resistant Klebsiella pneumoniae ST11 in China

• Published in: Nature communications Vol. 14; no. 1; p. 2464
• Main Authors: Zhou, Kai, Xue, Chun-Xu, Xu, Tingting, Shen, Ping, Wei, Sha, Wyres, Kelly L., Lam, Margaret M. C., Liu, Jinquan, Lin, Haoyun, Chen, Yunbo, Holt, Kathryn E., Xiao, Yonghong
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 28.04.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 38/22; 38/23; 38/39; 38/77; 631/326/107; 631/326/22/1434; 692/699/255/1318; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Antibiotics; beta-Lactamases - genetics; Carbapenem-Resistant Enterobacteriaceae - genetics; Carbapenems; China - epidemiology; Epidemics; Gene sequencing; Genomic analysis; Humanities and Social Sciences; Humans; Klebsiella; Klebsiella Infections - drug therapy; Klebsiella Infections - epidemiology; Klebsiella pneumoniae; Klebsiella pneumoniae - genetics; multidisciplinary; Multidrug resistance; Mutation; Phagocytosis; Point Mutation; Public health; Recombination; Science; Science (multidisciplinary); Sulfamethoxazole; Trimethoprim; Virulence; China
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-023-38061-z

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. Authors carry out a genomic analysis of carbapenem-resistant Klebsiella pneumoniae bloodstream isolates, noting subclonal expansion, associated with the emergence of a hypervirulent subpopulation.