title: Prediction of the mechanism of action of fusaricidin on Bacillus subtilis.
abstract: Long-term use of antibiotics has engendered a large number of resistant pathogens, which pose a serious threat to human health. Here, we investigated the mechanism of fusaricidin antibacterial activity toward Bacillus subtilis and characterized the pathways responsible for drug resistance. We found that σ(w), an extracytoplasmic function sigma factor, plays an important role in the resistance to fusaricidins during the initial 5 minutes of drug addition. Approximately 18 genes were induced more than 3-fold, of which 66.7% are known to be regulated by σ(w). Over the following 3 h, fusaricidins induced 194 genes more than three-fold, and most were associated with classes of antibiotic-responsive stimulons. Moreover, the fusaricidin treatment increased the catabolism of fatty and amino acids but strongly repressed glucose decomposition and gluconeogenesis. In summary, our data provide insight into the mechanism of fusaricidin activity, on which we based our suggested strategies for the development of novel antibiotic agents.
authors.affiliation: Lab of Biosystems and Microanalysis, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Wen-Bang
authors.initials: WB
authors.lastname: Yu
authors.forename: Chun-Yun
authors.initials: CY
authors.lastname: Yin
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Bang-Ce
authors.initials: BC
authors.lastname: Ye
mesh_terms: D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D001578:Benzopyrans / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects; D006801:Humans; D011401:Promoter Regions, Genetic; D011728:Pyridones / Q000494:pharmacology*; D012808:Sigma Factor / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001578:Benzopyrans; D011728:Pyridones; D012808:Sigma Factor; C103980:fusaricide