title: Examine the characterization of biofilm formation and inhibition by targeting SrtA mechanism in Bacillus subtilis: a combined experimental and theoretical study.
abstract: Bacillus subtilis is one of the well-known biofilm-forming organisms associated with plants, animals, and also used as a model organism for all Bacillus sp. In B. subtilis, SrtA enzyme plays the imperative roles in mechanism of signaling pathway and microbial adherence toward the host. SrtA is highly considered as a universal drug target for all Gram positive pathogens. Because of unresolved 3D structure of SrtA in Gram positive bacteria including B. subtilis, we developed a homology model protein using structural alignments of similar SrtA from B. anthracis. While the structural model of SrtA is analyzed because of its significance in biofilm formation by screening the suitable active site based compounds and analyzing the ability of bacterial biofilm inhibition. Druggability site based screening able to retrieve the active compounds against SrtA and checked the activity of the screened compounds through experimental biochemical assays and in situ microscopic analysis. Here in this study we concluded the computationally screened SrtA inhibitors showed high level of biofilm inhibition despite difficulties in bacterial membrane rigidification. Hence this study leads a way to the new compounds that may be useful to treat the bacterial infections.
authors.affiliation: Computer Aided Drug Design and Molecular Modeling Lab, Department of Bioinformatics, Alagappa University, Karaikudi, 630 004, Tamil Nadu, India.
authors.forename: Chandrabose
authors.initials: C
authors.lastname: Selvaraj
authors.forename: Jeyachandran
authors.initials: J
authors.lastname: Sivakamavalli
authors.forename: Baskaralingam
authors.initials: B
authors.lastname: Vaseeharan
authors.forename: Poonam
authors.initials: P
authors.lastname: Singh
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Singh
mesh_terms: D000595:Amino Acid Sequence; D019881:Aminoacyltransferases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D001412:Bacillus subtilis / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology* / Q000648:ultrastructure; D001422:Bacterial Adhesion / Q000187:drug effects; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D018441:Biofilms / Q000187:drug effects / Q000254:growth & development*; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D011135:Polysaccharides, Bacterial / Q000378:metabolism; D017433:Protein Structure, Secondary; D015203:Reproducibility of Results; D017550:Spectroscopy, Fourier Transform Infrared; D040681:Structural Homology, Protein; D013816:Thermodynamics
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D011135:Polysaccharides, Bacterial; D019881:Aminoacyltransferases; C120542:sortase A; D003546:Cysteine Endopeptidases