Shen Zhangqi, Patil Rocky D, Sahin Orhan, Wu Zuowei, Pu Xiao-Ying, Dai Lei, Plummer Paul J, Yaeger Michael J, Zhang Qijing
Department of Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, IA, 50011, USA.
Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University, Ames, IA, 50011, USA.
Mol Microbiol. 2016 Sep;101(6):909-23. doi: 10.1111/mmi.13431. Epub 2016 Jul 4.
Toxin-antitoxin (TA) systems are widely distributed in bacteria and play an important role in maintaining plasmid stability. The leading foodborne pathogen, Campylobacter jejuni, can carry multiple plasmids associated with antibiotic resistance or virulence. Previously a virulence plasmid named pVir was identified in C. jejuni 81-176 and IA3902, but determining the role of pVir in pathogenesis has been hampered because the plasmid cannot be cured. In this study, we report the identification of two TA systems that are located on the pVir plasmid in 81-176 and IA3902, respectively. The virA (proteic antitoxin)/virT (proteic toxin) pair in IA3902 belongs to a Type II TA system, while the cjrA (RNA antitoxin)/cjpT (proteic toxin) pair in 81-176 belongs to a Type I TA system. Notably, cjrA (antitoxin) represents the first noncoding small RNA demonstrated to play a functional role in Campylobacter physiology to date. By inactivating the TA systems, pVir was readily cured from Campylobacter, indicating their functionality in Campylobacter. Using pVir-cured IA3902, we demonstrated that pVir is not required for abortion induction in the guinea pig model. These findings establish the key role of the TA systems in maintaining plasmid stability and provide a means to evaluate the function of pVir in Campylobacter pathobiology.
毒素-抗毒素(TA)系统广泛分布于细菌中,在维持质粒稳定性方面发挥着重要作用。主要的食源性病原体空肠弯曲菌可携带多个与抗生素抗性或毒力相关的质粒。此前,在空肠弯曲菌81-176和IA3902中鉴定出一种名为pVir的毒力质粒,但由于该质粒无法消除,确定pVir在发病机制中的作用受到了阻碍。在本研究中,我们报告分别在81-176和IA3902的pVir质粒上鉴定出两个TA系统。IA3902中的virA(蛋白质抗毒素)/virT(蛋白质毒素)对属于II型TA系统,而81-176中的cjrA(RNA抗毒素)/cjpT(蛋白质毒素)对属于I型TA系统。值得注意的是,cjrA(抗毒素)是迄今为止第一个被证明在空肠弯曲菌生理学中发挥功能作用的非编码小RNA。通过使TA系统失活,pVir很容易从空肠弯曲菌中消除,表明它们在空肠弯曲菌中的功能。使用消除pVir的IA3902,我们证明在豚鼠模型中诱导流产不需要pVir。这些发现确立了TA系统在维持质粒稳定性中的关键作用,并提供了一种评估pVir在空肠弯曲菌病理生物学中功能的方法。