Zhang Feilong, Li Zhihua, Li Ziyao, Liu Xinmeng, Lei Zichen, Zhuo Xianxia, Yang Xinrui, Zhao Jiankang, Zhang Yulin, Lu Binghuai
Peking Union Medical College, Chinese Academy of Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
National Center for Respiratory Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, National Clinical Research Center for Respiratory Diseases, Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Laboratory of Clinical Microbiology and Infectious Diseases, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing, China.
Commun Biol. 2024 Dec 2;7(1):1602. doi: 10.1038/s42003-024-07310-2.
The rise of the convergence of hypervirulence and carbapenem resistance in Klebsiella pneumoniae has been increasingly reported in recent years, however, there are few outbreak cases for these producing NDM carbapenemase. In this study, ST65-KL2 and ST11-KL64 hypervirulent and carbapenem-resistant K. pneumoniae (hvCRKP) were identified from two different outbreak cases: (1) clonal spreading of ST65-KL2 in five patients within transplantation wards spanning three months; and (2) clonal transmission of ST11-KL64 in ten patients across 10 months. The representative strains of ST65-KL2 and ST11-KL64 hvCRKP, K22877 and K56649, produced carbapenemase NDM-5 and dual carbapenemases KPC-2 and NDM-13, respectively, and both exhibited high-level carbapenem resistance. Moreover, virulent analysis showed that K22877 and K56649 were hypervirulent and the former possessed stronger virulence. Evolutionary pathways suggested ST65-KL2 and ST11-KL64 hvCRKP could be classified as CR-hvKP (hvKP acquiring carbapenem resistance) and hv-CRKP (CRKP acquiring hypervirulence), respectively. Unexpectedly, ST65-KL2 CR-hvKP showed resistance to ciprofloxacin mediated by plasmid acquisition as its spread, and ST11-KL64 hv-CRKP developed into enhanced virulence and macrophage resistance. Furthermore, compared to the ST65-KL2 CR-hvKP, the ST11-KL64 hv-CRKP tends to cause occult and persistent infection. Global genome analysis revealed ST11-KL64 hv-CRKP and ST65-KL2 CR-hvKP mainly carried bla and had significant differences in Ompk35/36, ybt, resistance and virulence. Effective surveillance should be implemented and novel therapeutic strategies are urgently needed to deal with refractory infections.
近年来，肺炎克雷伯菌中高毒力与碳青霉烯耐药性融合的情况越来越多地被报道，然而，产NDM碳青霉烯酶的暴发案例却很少。在本研究中，从两起不同的暴发案例中鉴定出ST65-KL2和ST11-KL64高毒力且耐碳青霉烯的肺炎克雷伯菌（hvCRKP）：（1）ST65-KL2在三个月内于移植病房的五名患者中克隆传播；（2）ST11-KL64在十个月内于十名患者中克隆传播。ST65-KL2和ST11-KL64 hvCRKP的代表性菌株K22877和K56649分别产生碳青霉烯酶NDM-5和双碳青霉烯酶KPC-2和NDM-13，且二者均表现出高水平的碳青霉烯耐药性。此外，毒力分析表明K22877和K56649具有高毒力，且前者的毒力更强。进化途径表明ST65-KL2和ST11-KL6?hvCRKP可分别归类为CR-hvKP（高毒力肺炎克雷伯菌获得碳青霉烯耐药性）和hv-CRKP（耐碳青霉烯肺炎克雷伯菌获得高毒力）。出乎意料的是，ST65-KL2 CR-hvKP在传播过程中通过获得质粒介导对环丙沙星耐药，而ST11-KL64 hv-CRKP的毒力和巨噬细胞耐药性增强。此外，与ST65-KL2 CR-hvKP相比，ST11-KL64 hv-CRKP更易引发隐匿性和持续性感染。全基因组分析显示，ST11-KL64 hv-CRKP和ST65-KL2 CR-hvKP主要携带bla，且在Ompk35/36、ybt、耐药性和毒力方面存在显著差异。应实施有效的监测，并且迫切需要新的治疗策略来应对难治性感染。
