Screening of Novel Drug Targets and Drug Design for Bordetella pertussis: A Subtractive Proteomics Approach.

Bordetella pertussis causes whooping cough in humans that spreads directly from individual to individual mainly by aerosolized respiratory droplets. Nowadays, it gained the attention of scientific community because it has already been reemerged as one of the major public health threats despite widespread vaccination efforts. Moreover, the growing antibiotic resistance has made it difficult to combat this pathogen with currently available antibiotics. Consequently, screening drug targets and discovering drugs against unique proteins of the pathogen could be a promising alternative. With this view, 3,359 proteins of B. pertussis were screened in silico to identify non-duplicate proteins crucial for survival of the bacteria, non-homologous to humans, involved in unique metabolic pathways of the pathogen, and conserved among various bacterial strains. Among these, Chemotaxis protein Mota, Chromosomal replication initiator protein DnaA, Short-chain fatty acids transporter, [protein-PII] uridylyltransferase, Type III secretion protein V, Potassium-transporting ATPase potassium-binding subunit, N-acetylmuramoyl-L-alanine amidase, and RNA polymerase sigma-54 factor fulfilled these criteria. These proteins were further analyzed for qualitative characteristics such as virulence properties and associations with antibiotic resistance, etc. In addition, plant metabolites were screened against these unique proteins utilizing molecular docking to discover putative drugs against them. Four metabolites exhibited superior binding affinity and favorable ADME (Adsorption, distribution, metabolism, and excretion) properties which can further be tested in vivo.