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

Kai Zhou (), Chun-Xu Xue, Tingting Xu, Ping Shen, Sha Wei, Kelly L. Wyres, Margaret M. C. Lam, Jinquan Liu, Haoyun Lin, Yunbo Chen, Kathryn E. Holt and Yonghong Xiao ()
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Kai Zhou: Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)
Chun-Xu Xue: Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)
Tingting Xu: Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)
Ping Shen: Zhejiang University School of Medicine
Sha Wei: Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)
Kelly L. Wyres: Monash University
Margaret M. C. Lam: Monash University
Jinquan Liu: Jinan University; The First Affiliated Hospital, Southern University of Science and Technology)
Haoyun Lin: Shenzhen People’s Hospital
Yunbo Chen: Zhejiang University School of Medicine
Kathryn E. Holt: Monash University
Yonghong Xiao: Zhejiang University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-38061-z

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