Identification and functional analysis of two toxin–antitoxin systems in Campylobacter jejuni

• Published in: Molecular microbiology 2016-09, Vol.101 (6), p.909-923
• Main Authors: Shen, Zhangqi, Patil, Rocky D., Sahin, Orhan, Wu, Zuowei, Pu, Xiao‐Ying, Dai, Lei, Plummer, Paul J., Yaeger, Michael J., Zhang, Qijing
• Format: Article
• Language: English
• Subjects: Animals; Antitoxins - genetics; Antitoxins - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Bacterial Toxins - genetics; Bacterial Toxins - metabolism; Bacteriology; Campylobacter Infections - microbiology; Campylobacter jejuni; Campylobacter jejuni - genetics; Campylobacter jejuni - metabolism; Chromosomes, Bacterial; Disease Models, Animal; Food contamination & poisoning; Guinea Pigs; Pathogens; Plasmids; Plasmids - genetics; Poultry
• ISSN: 0950-382X; 1365-2958
• DOI: 10.1111/mmi.13431

Summary 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. Campylobacter jejuni is a major zoonotic pathogen. Here we present the first identification of toxin‐antitoxin (TA) systems in this organism, which play an important role in maintaining the stability of virulence plasmid pVir. Both toxins are proteic and inhibit cell growth by degrading cellular mRNA. Antitoxin VirA neutralizes toxin VirT by protein‐protein interaction, while antitoxin cjrA detoxifies toxin CjpT by binding to its mRNA.