title: Proteomics analyses of Bacillus subtilis after treatment with plumbagin, a plant-derived naphthoquinone.
abstract: Infectious diseases and increasing antibiotic resistance among diverse classes of microbes are global health concerns and a prime focus of omics systems science applications in novel drug discovery. Plumbagin is a plant-derived naphthoquinone, a natural product that exhibits antibacterial activity against gram-positive bacteria. In the present study, we investigated the antimicrobial effects of plumbagin against Bacillus subtilis using two complementary proteomics techniques: two-dimensional electrophoresis (2-DE) and isobaric tag for relative and absolute quantification (iTRAQ). Comparative quantitative proteomics analysis of plumbagin treated and untreated control samples identified differential expression of 230 proteins (1% FDR, 1.5 fold-change and ≥2 peptides) in B. subtilis after plumbagin treatment. Pathway analysis involving the differentially expressed proteins suggested that plumbagin effectively increases heme and protein biosynthesis, whereas fatty acid synthesis was significantly reduced. Gene expression and metabolic activity assays further corroborated the proteomics findings. We anticipate that plumbagin blocks the cell division by altering the membrane permeability required for energy generation. This is the first report, to the best of our knowledge, offering new insights, at proteome level, for the putative mode(s) of action of plumbagin and attendant cellular targets in B. subtilis. The findings also suggest new ways forward for the modern omics-guided drug target discovery, building on traditional plant medicine.
authors.affiliation: 1 Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Powai, Mumbai, India .
authors.forename: Panga Jaipal
authors.initials: PJ
authors.lastname: Reddy
authors.forename: Sandipan
authors.initials: S
authors.lastname: Ray
authors.forename: Gajanan J
authors.initials: GJ
authors.lastname: Sathe
authors.forename: T S Keshava
authors.initials: TS
authors.lastname: Prasad
authors.forename: Srikanth
authors.initials: S
authors.lastname: Rapole
authors.forename: Dulal
authors.initials: D
authors.lastname: Panda
authors.forename: Sanjeeva
authors.initials: S
authors.lastname: Srivastava
mesh_terms: D001412:Bacillus subtilis / Q000187:drug effects* / Q000378:metabolism*; D009285:Naphthoquinones / Q000494:pharmacology*; D040901:Proteomics / Q000379:methods*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D009285:Naphthoquinones; C014758:plumbagin