a toxin-antitoxin module in bacillus subtilis can both mitigate and amplify effects of lethal stresstoxin-antitoxin模块在枯草芽孢杆菌可以减轻和放大致命的压力的影响.pdfVIP

A Toxin-Antitoxin Module in Bacillus subtilis Can Both Mitigate and Amplify Effects of Lethal Stress Xiangli Wu1,2¤, Xiuhong Wang1,3, Karl Drlica1,4, Xilin Zhao1,4* 1 Public Health Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America, 2 State Key Laboratory for Agrobiotechnology and Department of Microbiology, China Agricultural University, Beijing, China, 3 Department of Biochemistry, Harbin Medical University, Harbin, Heilongjiang Province, China, 4 Department of Microbiology Molecular Genetics, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America Abstract Background: Bacterial type-2 (protein-protein) toxin-antitoxin (TA) modules are two-gene operons that are thought to participate in the response to stress. Previous work with Escherichia coli has led to a debate in which some investigators conclude that the modules protect from stress, while others argue that they amplify lethal stress and lead to programmed cell death. To avoid ambiguity arising from the presence of multiple TA modules in E. coli, the effect of the sole type-2 toxin- antitoxin module of Bacillus subtilis was examined for several types of lethal stress. Methodology/Principal Findings: Genetic knockout of the toxin gene, ndoA (ydcE), conferred protection to lethal stressors that included kanamycin, moxifloxacin, hydrogen peroxide, and UV irradiation. However, at low doses of UV irradiation the ndoA deficiency increased lethality. Indeed, gradually increasing UV dose with the ndoA mutant revealed a crossover response – from the mutant being more sensitive than wild-type cells to being less sensitive. For high temperature and nutrient starvation, the toxin deficiency rendered cells hyper