Carbapenem-resistant Citrobacter freundii harboring blaKPC−2 and blaNDM−1: a study on their transferability and potential dissemination via generating a transferrable hybrid plasmid mediated by IS6100

Frontiers in Microbiology

Microbiology

Yanyan Fan¹  Yulin Zhang¹  Jiankang Zhao¹  Ziyao Li²  Zichen Lei²  Xinrui Yang³  Yongli Wu³  Yanning Hu⁴  Zhihua Li⁴  Xinmeng Liu⁴  Feilong Zhang⁴  Binghuai Lu⁵  Chen Li⁶ 

[1] Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China;Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China;Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China;Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China;China-Japan Friendship Institute of Clinical Medical Sciences, Beijing, China;Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China;Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China;Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China;Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China;Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China;Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China;Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China;Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China;Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China;China-Japan Friendship Institute of Clinical Medical Sciences, Beijing, China;Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China;Peking University China-Japan Friendship School of Clinical Medicine, Beijing, China;Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, National Clinical Research Center for Respiratory Diseases, National Center for Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China;Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing, China;Liuyang Traditional Chinese Medicine Hospital, Changsha, Hunan, China;

关键词: Citrobacter freundii;    KPC-2- and NDM-1-coproducing CRCF;    hybrid plasmid;    transposition recombination;    6100;   

DOI  :  10.3389/fmicb.2023.1239538

 received in 2023-06-13, accepted in 2023-07-31,  发布年份 2023

来源: Frontiers

【 摘 要 】

IntroductionThe increase in clinical Enterobacteriaceae with dual carbapenemase has become a serious healthcare concern. It is essential to characterize the transferability and potential dissemination of blaKPC−2- and blaNDM−1-coharboring carbapenem-resistant Citrobacter freundii (CRCF).MethodsFour blaKPC−2- and blaNDM−1-coharboring CRCF strains were collected from our surveillance of the prevalence of carbapenem-resistant Enterobacteriaceae. The isolates were assessed using species identification, antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing, plasmid stability, and fitness costs. Clonality, genome, plasmidome, and phylogeny were analyzed to reveal potential dissemination.ResultsThree ST523 blaKPC−2- and blaNDM−1-coharboring CRCF strains, collected from the same hospital within 1 month, exhibited high homology (both identity and coverage >99%), implying clonal dissemination and a small-scale outbreak. Moreover, the blaKPC−2 and blaNDM−1 genes were coharbored on an IncR plasmid, probably generated by a blaKPC−2-harboring plasmid acquiring blaNDM−1, in these three strains. Importantly, the IncR plasmid may form a transferable hybrid plasmid, mediated by IS6100 via transposition, with another IncFII plasmid included in the same C. freundii strain. Furthermore, the blaKPC−2 and blaNDM−1 of the fourth CRCF strain are located on two different non-transferable plasmids lacking complete transfer elements. Additionally, throughout the course of the 10-day continuous passage, the genetic surroundings of blaNDM−1 in four CRCF strains were gradually excised from their plasmids after the 8th day, whereas they maintained 100% retention for blaKPC−2. Genome and plasmidome analyses revealed that blaKPC−2- or blaNDM−1-harboring C. freundii were divergent, and these plasmids have high homology to plasmids of other Enterobacteriaceae.ConclusionClonal dissemination of ST523 blaKPC−2- and blaNDM−1-coharboring CRCF strains was detected, and we first reported blaKPC−2 and blaNDM−1 concomitantly located on one plasmid, which could be transferred with mediation by IS6100 via transposition. Continued surveillance should urgently be implemented.

【 授权许可】

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Copyright © 2023 Zhang, Li, Liu, Hu, Zhao, Zhang, Fan, Lei, Yang, Li, Li, Wu and Lu.