title: Identification and characterization of potential drug targets by subtractive genome analyses of methicillin resistant Staphylococcus aureus.
abstract: Methicillin resistant Staphylococcus aureus (MRSA) causes serious infections in humans and becomes resistant to a number of antibiotics. Due to the emergence of antibiotic resistance strains, there is an essential need to develop novel drug targets to address the challenge of multidrug-resistant bacteria. In current study, the idea was to utilize the available genome or proteome in a subtractive genome analyses protocol to identify drug targets within two of the MRSA types, i.e., MRSA ST398 and MRSA 252. Recently, the use of subtractive genomic approaches helped in the identification and characterization of novel drug targets of a number of pathogens. Our protocol involved a similarity search between pathogen and host, essentiality study using the database of essential genes, metabolic functional association study using Kyoto Encyclopedia of Genes and Genomes database (KEGG), cellular membrane localization analysis and Drug Bank database. Functional family characterizations of the identified non homologous hypothetical essential proteins were done by SVMProt server. Druggability potential of each of the identified drug targets was also evaluated by Drug Bank database. Moreover, metabolic pathway analysis of the identified druggable essential proteins with KEGG revealed that the identified proteins are participating in unique and essential metabolic pathways amongst MRSA strains. In short, the complete proteome analyses by the use of advanced computational tools, databases and servers resulted in identification and characterization of few nonhomologous/hypothetical and essential proteins which are not homologous to the host genome. Therefore, these non-homologous essential targets ensure the survival of the pathogen and hence can be targeted for drug discovery.
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. Electronic address: mriazuddin@iccs.edu.
authors.forename: Reaz
authors.initials: R
authors.lastname: Uddin
authors.affiliation: Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
authors.forename: Kiran
authors.initials: K
authors.lastname: Saeed
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins / Q000737:chemistry / Q000378:metabolism; D030562:Databases, Protein; D055808:Drug Discovery; D016680:Genome, Bacterial; D006801:Humans; D053858:Metabolic Networks and Pathways; D055624:Methicillin-Resistant Staphylococcus aureus / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D011770:Pyruvate Kinase / Q000737:chemistry / Q000378:metabolism; D017385:Sequence Homology
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D011770:Pyruvate Kinase
keywords: Druggability; Methicillin resistant; Proteome; S. aureus; Subtractive genome