title: Physical and Functional Interplay between MazF1Bifand Its Noncognate Antitoxins from Bifidobacterium longum.
abstract: Bifidobacterium longumstrain JDM301, a widely used commercial strain in China, encodes at least two MazEF-like modules and one RelBE-like toxin-antitoxin (TA) system in its chromosome, designated MazE1F1Bif, MazE2F2Bif, and RelBEBif, respectively. Bacterial TA systems play an important role in several stress responses, but the relationship between these TA systems is largely unknown. In this study, the interactions between MazF1Bifand MazE2Bifor RelBBifwere assessed inB. longumstrain JDM301. MazF1Bifcaused the degradation oftufABifmRNA, and its toxicity was inhibited by forming a protein complex with its cognate antitoxin, MazE1BifNotably, MazF1Biftoxicity was also partially neutralized when jointly expressed with noncognate antitoxin MazE2Bifor RelBBifOur results show that the two noncognate antitoxins also inhibited mRNA degradation caused by MazF1Biftoxin. Furthermore, the physical interplay between MazF1Bifand its noncognate antitoxins was confirmed by immunoprecipitation. These results suggest that MazF1Bifcan arrest cell growth and that MazF1Biftoxicity can be neutralized by its cognate and noncognate antitoxins. These results imply that JDM301 uses a sophisticated toxin-antitoxin interaction network to alter its physiology when coping with environmental stress.IMPORTANCEAlthough toxin-antitoxin (TA) systems play an important role in several stress responses, the regulatory mechanisms of multiple TA system homologs in the bacterial genome remain largely unclear. In this study, the relationships between MazE1F1Bifand the other two TA systems ofBifidobacterium longumstrain JDM301 were explored, and the interactions between MazF1Bifand MazE2Bifor RelBBifwere characterized. In addition, the mRNA degradation activity of MazF1Bifwas demonstrated. In particular, the interaction of the toxin with noncognate antitoxins was shown, even between different TA families (MazF1Biftoxin and RelBBifantitoxin) in JDM301. This work provides insight into the regulatory mechanisms of TA systems implicated in the stress responses of bifidobacteria.
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.|Jiangsu Vocational College of Nursing, Huaian, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
authors.forename: Dianbin
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Hua
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
authors.forename: Yugang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China ZKY02@163.com tangrenxian-t@163.com.
authors.forename: Kuiyang
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Department of Pathogenic Biology and Immunology, Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China ZKY02@163.com tangrenxian-t@163.com.
authors.forename: Renxian
authors.initials: R
authors.lastname: Tang
mesh_terms: D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000069978:Bifidobacterium longum / Q000378:metabolism*; D047468:Immunoprecipitation; D009500:Neutralization Tests; D011485:Protein Binding; D020871:RNA Stability
chemical_list: D001427:Bacterial Toxins
keywords: Bifidobacterium longum; cross-interaction; mRNA degradation; toxin-antitoxin system