Identification of potential drug targets in human pathogen Bacillus cereus and insight for finding inhibitor through subtractive proteome and molecular docking studies

Abstract

Bacillus cereus is a gram-positive, anaerobic, spore-forming bacterium related to food poisoning in humans. Vomit and diarrhea are the symptoms of foodborne B. cereus infection caused by emetic toxins and three enterotoxins, respectively. This bacterium is broadly present in soil and foods such as vegetables, spices, milk, and meat. The antibiotics impenem, vancomycin, chloramphenicol, gentamicin, and ciprofloxacin are used for all susceptible strains of B. cereus. But these antibiotics cause side effects in the host due to the drug-host interaction; because the targeted proteins by the drugs are not pathogen specific proteins, they are similar to human proteins also. To overcome this problem, this study focused on identifying putative drug targets in the pathogen B. cereus and finding new drugs to inhibit the function of the pathogen. The identification of drug targets is a pipeline process, starting with the identification of targets non-homologous to human and gutmicrobiota proteins, finding essential proteins, finding other proteins that highly interact with these essential proteins that are also highly important for protein network stability, finding cytoplasmic proteins with a clear pathway and known molecular function, and finding non-druggable proteins. Through this process, two novel drug targets were identified in B. cereus. Among the various antibiotics, Gentamicin had showed good binding affinity with the identified novel targets through molecular modeling and docking studies using Prime and GLIDE module of Schrödinger. Hence, this study suggest that the identified novel drug targets may very useful in drug therapeutic field for finding inhibitors which are similar to Gentamicin and designing new formulation of drug molecules to control the function of the foodborne illness causing pathogen B. cereus.

Keywords: B. cereus; Druggability; Foodborne; Network analysis; Putative drug target.