Li Yan, Xu Lei, Li Yuhan, Wang Mianzhi, He Tao, Bai Li, Li Ruichao, Wang Zhiqiang
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, China; Institute of Comparative Medicine, Yangzhou University, Yangzhou, Jiangsu, China.
Int J Food Microbiol. 2023 Apr 16;391-393:110138. doi: 10.1016/j.ijfoodmicro.2023.110138. Epub 2023 Feb 15.
Tigecycline plays an important role in the clinical treatment of infections caused by multidrug-resistant pathogens. The emergence of plasmid-mediated tigecycline resistance genes tet(X) and tmexCD1-tmexJ1 has been reported in a variety of animal and animal-derived foods, and have the potential spread to humans, seriously limiting the choice of clinical medication. Herein, three ST92 Klebsiella michiganensis isolates co-harboring tet(X4) and tmexCD2-toprJ2 were collected from pork samples in Jiangsu Province, China. These K. michiganensis isolates were all multidrug-resistant isolates. Genome analysis showed that tmexCD2-toprJ2 and tet(X4) were located on IncFIB(K) and IncX1 plasmids, respectively. The IncFIB(K) plasmid pMX581-77k is a novel tmexCD2-toprJ2-bearing plasmid. Worryingly, there were only a small number of SNPs between K. michiganensis isolated from pork in this study and K. michiganensis from human sources, with the possibility of clonal transmission. In addition, tet(X4) and tmexCD2-toprJ2 in K. michiganensis were able to stabilize in the absence of antibiotics. The growth curve indicated that the tmexCD2-toprJ2-positive plasmid imposed a burden on the growth of host bacteria. Interestingly, we found that the high-level resistance phenotype to tigecycline in these K. michiganensis isolates was mainly mediated by tet(X4). However, both tet(X4) and tmexCD2-toprJ2 expression were significantly elevated when host bacteria were exposed to tigecycline. This study systematically investigated K. michiganensis co-carrying tet(X4) and tmexCD2-toprJ2, emphasizing the importance for continuous surveillance of tigecycline-resistant K. michiganensis in animal-derived foods.
替加环素在耐多药病原体引起的感染临床治疗中发挥着重要作用。已在多种动物及动物源性食品中报道了质粒介导的替加环素耐药基因tet(X)和tmexCD1-tmexJ1的出现，并且有传播至人类的可能性，这严重限制了临床用药的选择。在此，从中国江苏省的猪肉样本中收集到三株共携带tet(X4)和tmexCD2-toprJ2的密歇根克雷伯菌分离株。这些密歇根克雷伯菌分离株均为耐多药分离株。基因组分析表明，tmexCD2-toprJ2和tet(X4)分别位于IncFIB(K)和IncX1质粒上。IncFIB(K)质粒pMX581-77k是一种携带tmexCD2-toprJ2的新型质粒。令人担忧的是，本研究中从猪肉中分离出的密歇根克雷伯菌与来自人类的密歇根克雷伯菌之间仅有少量单核苷酸多态性，存在克隆传播的可能性。此外，密歇根克雷伯菌中的tet(X4)和tmexCD2-toprJ2在无抗生素的情况下能够稳定存在。生长曲线表明，携带tmexCD2-toprJ2的阳性质粒对宿主细菌的生长造成了负担。有趣的是，我们发现这些密歇根克雷伯菌分离株对替加环素的高水平耐药表型主要由tet(X4)介导。然而，当宿主细菌暴露于替加环素时，tet(X4)和tmexCD2-toprJ2的表达均显著升高。本研究系统地调查了共携带tet(X4)和tmexCD2-toprJ2的密歇根克雷伯菌，强调了持续监测动物源性食品中耐替加环素密歇根克雷伯菌的重要性。
