Emergence and plasmid cointegration-based evolution of NDM-1-producing ST107 Citrobacter freundii high-risk resistant clone in China

• Published in: International journal of antimicrobial agents 2024-02, Vol.63 (2), p.107069-107069, Article 107069
• Main Authors: Liu, Haiyang, Tu, Yuexing, He, Jintao, Xu, Qingye, Zhang, Xiaofan, Mu, Xinli, Chen, Minhua, Zhou, Hua, Li, Xi
• Format: Article
• Language: English
• Subjects: Carbapenem-resistant Citrobacter freundii; Fitness; Plasmid evolution; St107; tmexCD2-toprJ2
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2023.107069

•An emerging carbapenem-tigecycline resistance clone of ST107 CRCF was reported.•One ST107 CRCF coharboring blaNDM-1, blaKPC-2 and tmexCD2-toprJ2.•Cointegrate plasmid pCF1807–2 possesses higher transfer efficiency and no fitness cost. Carbapenem-resistant Citrobacter freundii (CRCF) poses an enormous challenge in the health care setting. However, the epidemiology and plasmid dynamic evolution of this species have not been well studied, especially for the novel high-risk resistant clones in the intensive care units (ICUs). Here, we characterised the cointegration-based plasmid dynamic evolution of the emerging ST107 CRCF clone in China. Twenty CRCF strains were identified, including ST22 (30%), ST107 (25%), ST396 (10%) and ST116 (10%). Interestingly, the tigecycline (TGC) resistance gene cluster tmexCD2-toprJ2 and blaNDM-1 and blaKPC-2 were simultaneously found in one ST107 strain. Epidemiological analysis showed that ST107 clone contained human- and environment-derived strains from five countries. Notably, 93.75% (15/16) of the isolates harboured blaNDM-1 or blaKPC-2. Plasmid fusion among various ST107 strains of two patients occurred in the same ICU, mediated by Tn5403 and IS26-based insertion and deletion events. pCF1807–2 carried blaNDM-1 while pCF1807–3 carried both tmexCD2-toprJ2 and blaKPC-2 in the CF1807 strain. Importantly, the cointegrate plasmid pCF1807–2 exhibited higher transfer efficiency and could remain stable after serial passage. Notably, no fitness cost was observed for the host. In conclusion, ST107 CRCF is a high-risk resistant clone due to its ability to integrate resistant plasmids. Our findings elucidated the potential threat and global transmission of the ST107 lineage, and reasonable monitoring should be performed to prevent its further spread in hospitals. [Display omitted]