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.

Computational Identification of Putative Drug Targets in Malassezia Globosa by Subtractive Genomics and Protein Cluster Network Approach

“…Five unique pathways of M. globosa are carbapenem biosynthesis, various types of N-glycon biosynthesis, C-5 branched dibasic acid metabolisms, methane metabolism, sesquiterpenoid and triterpenoid biosynthesis. In this study, unique pathways have 29 enzymes of which 28 enzymes are involved in common pathways which is in accordance with the report [40] which stated that common drug targets are also involved in the pathway unique to the pathogens of bacterial meningitis. Also, the number of drug targets identified from the common pathways of M. globosa were more than that identified among Streptococcus pneumonia, Neisseria meningitidis, Haemophilus influenzae type b and Staphylococcus aureus causing bacterial meningitis.…”

Plasma metabolomics for the diagnosis and prognosis of H1N1 influenza pneumonia

“…In addition, elevated inositol phosphate metabolism has been observed with Pneumocystis pneumonia [ 34 ] and S. aureus infection in type II alveolar epithelial cells [ 35 ]. Methane metabolism pathways have been shown to be elevated in bacterial meningitis caused by pathogenesis of different species, such as S. pneumoniae , N. meningitis , Haemophilus influenzae , and S. aureus [ 36 ].…”

Identification of Putative Drug Targets and Vaccine Candidates for Pathogens Causing Atherosclerosis

“…It catalyzes the condensation reaction of fatty acid synthesis by the addition to an acyl acceptor of two carbons from malonyl-ACP. Substrate specificity of fabH determines the biosynthesis of branched-chain and/or straightchain of fatty acids [45]. FabH catalyses two stages such as acetyl Co-A condensation and malonyl-ACP decarboxylase reaction, blocking the ping-pong reaction of fabH will prevent the fatty acid biosynthesis.…”

“…FabH catalyses two stages such as acetyl Co-A condensation and malonyl-ACP decarboxylase reaction, blocking the ping-pong reaction of fabH will prevent the fatty acid biosynthesis. The enzyme is also reported as potential drug target against Streptococcus pneumonia, Neisseria meningitides, Haemophilys influnzae, Staphylococcus aureus, Enterococcus faecalis, Streptococcus mitis, Bortonella quintana, Coxiella burnetti, Legionella pneumopholi, Brucella melitensis and Biovar abartus [13,45].…”