title: Metabolic pathway analysis of S. pneumoniae: an in silico approach towards drug-design.
abstract: The emergence of multidrug resistant varieties of Streptococcus pneumoniae (S. pneumoniae) has led to a search for novel drug targets. An in silico comparative analysis of metabolic pathways of the host Homo sapiens (H. sapiens) and the pathogen S. pneumoniae have been performed. Enzymes from the biochemical pathways of S. pneumoniae from the KEGG metabolic pathway database were compared with proteins from the host H. sapiens, by performing a BLASTp search against the non-redundant database restricted to the H. sapiens subset. The e-value threshold cutoff was set to 0.005. Enzymes, which do not show similarity to any of the host proteins, below this threshold, were filtered out as potential drug targets. Five pathways unique to the pathogen S. pneumoniae when compared to the host H. sapiens have been identified. Potential drug targets from these pathways could be useful for the discovery of broad-spectrum drugs. Potential drug targets were also identified from pathways related to lipid metabolism, carbohydrate metabolism, amino acid metabolism, energy metabolism, vitamin and cofactor biosynthetic pathways and nucleotide metabolism. Of the 161 distinct targets identified from these pathways, many are in various stages of progress at the Microbial Genome Database. However, 44 of the targets are new and can be considered for rational drug design. The study was successful in listing out potential drug targets from the S. pneumoniae proteome involved in vital aspects of the pathogen's metabolism, persistence, virulence and cell wall biosynthesis. This systematic evaluation of metabolic pathways of host and pathogen through reliable and conventional bioinformatics approach can be extended to other pathogens of clinical interest.
authors.affiliation: Center for Energy Studies, Indian Institute of Technology Delhi, Hauz Khas, New Delhi-110016, India. shailza_iitd@yahoo.com
authors.forename: Shailza
authors.initials: S
authors.lastname: Singh
authors.forename: B K
authors.initials: BK
authors.lastname: Malik
authors.forename: D K
authors.initials: DK
authors.lastname: Sharma
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D001665:Binding Sites; D003198:Computer Simulation; D015195:Drug Design; D006801:Humans; D008954:Models, Biological; D011008:Pneumococcal Infections / Q000378:metabolism*; D011485:Protein Binding; D020543:Proteome / Q000378:metabolism*; D015398:Signal Transduction; D013296:Streptococcus pneumoniae / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D020543:Proteome