title: A toxin-antitoxin module in Bacillus subtilis can both mitigate and amplify effects of lethal stress.
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.
  
  
  RESULTS
  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 hypersensitive. The ndoA deficiency also reduced sporulation frequency, indicating a role for toxin-antitoxin modules in this developmental process. In the case of lethal antimicrobial treatment, deletion of the toxin eliminated a surge in hydrogen peroxide accumulation observed in wild-type cells.
  
  
  CONCLUSIONS
  A single toxin-antitoxin module can mediate two opposing effects of stress, one that lowers lethality and another that raises it. Protective effects are thought to arise from toxin-mediated inhibition of translation based on published work. The enhanced, stress-mediated killing probably involves toxin-dependent accumulation of reactive oxygen species, since a deficiency in the NdoA toxin suppressed peroxide accumulation following antimicrobial treatment. The type and perhaps the level of stress appear to be important for determining whether this toxin will have a protective or detrimental effect.
authors: Public Health Research Institute, New Jersey Medical School, University of Medicine and Dentistry of New Jersey, Newark, New Jersey, United States of America.
authors: Xiangli
authors: X
authors: Wu
authors: Xiuhong
authors: X
authors: Wang
authors: Karl
authors: K
authors: Drlica
authors: Xilin
authors: X
authors: Zhao
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000992:Antitoxins / Q000235:genetics*; D001372:Aza Compounds / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics* / Q000502:physiology* / Q000528:radiation effects; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001427:Bacterial Toxins / Q000235:genetics*; D024841:Fluoroquinolones; D005798:Genes, Bacterial / Q000235:genetics*; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D007612:Kanamycin / Q000494:pharmacology; D050296:Microbial Viability / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D000077266:Moxifloxacin; D009876:Operon / Q000235:genetics; D011804:Quinolines / Q000494:pharmacology; D013171:Spores, Bacterial / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D013312:Stress, Physiological / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D000900:Anti-Bacterial Agents; D000992:Antitoxins; D001372:Aza Compounds; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D024841:Fluoroquinolones; D011804:Quinolines; D007612:Kanamycin; D006861:Hydrogen Peroxide; D000077266:Moxifloxacin