In Silico Identification of Common Putative Drug Targets among the Pathogens of Bacterial Meningitis

Abstract

Monitoring infectious emerging diseases, especially the central nervous system infections, has become one of the important priorities in health care system. Epidemiological, serological and bacteriological studies revealed that Streptococcus pneumonia, Neisseria meningitidis, Haemophilus influenzae type b and Staphylococcus aureus are common pathogens of bacterial meningitis. Therefore, identification of common drug targets in these pathogens would be crucial to overcome drug resistance to existing antibiotic therapy. In the present study, comparative proteome analysis, subtractive genomic approach and metabolic pathway analysis were implemented to propose common potential drug targets for pathogens of bacterial meningitis. Streptococcus pneumonia was selected as reference organism, and the common proteins of the pathogens were verified for essentiality in pathogen’s survival, using Database of Essential Genes (DEG). The 213 essential proteins identified were screened for human non-homology. Thirty seven unique essential proteins which are non-homologues to human were proposed as common potential drug targets for pathogens of bacterial meningitis. Pathway analysis revealed that 26 drug targets were enzymes, eight were non-enzymes, and three were conserved hypothetical proteins. Six enzymes were involved in pathways unique to the pathogens of bacterial meningitis. Furthermore, prediction of sub cellular localization and drug prioritization of 37 proteins affirmed that the drug targets would be useful in design and discovery of novel therapeutic compounds against bacterial meningitis.