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Identification and modeling of a drug target for Clostridium perfringens SM101
Authors:Chhabra Gagan  Sharma Pramila  Anant Avishek  Deshmukh Sachin  Kaushik Himani  Gopal Keshav  Srivastava Nutan  Sharma Neeraj  Garg Lalit C
Institution:Gene Regulation Laboratory, National Institute of Immunology, Aruna Asaf Ali Marg, New Delhi – 110067, India.
Abstract:In the present study, comparative genome analysis between Clostridium perfringens and the human genome was carried out to identify genes that are essential for the pathogen's survival, and non-homologous to the genes of human host, that can be used as potential drug targets. The study resulted in the identification of 426 such genes. The number of these potential drug targets thus identified is significantly lower than the genome's protein coding capacity (2558 protein coding genes). The 426 genes of C. perfringens were further analyzed for overall similarities with the essential genes of 14 different bacterial species present in Database of Essential Genes (DEG). Our results show that there are only 5 essential genes of C. perfringens that exhibit similarity with 12 species of the 14 different bacterial species present in DEG database. Of these, 1 gene was similar in 12 species and 4 genes were similar in 11 species. Thus, the study opens a new avenue for the development of potential drugs against the highly pathogenic bacterium. Further, by selecting these essential genes of C. perfringens, which are common and essential for other pathogenic microbial species, a broad spectrum anti-microbial drug can be developed. As a case study, we have built a homology model of one of the potential drug targets, ABC transporter-ATP binding protein, which can be employed for in silico docking studies by suitable inhibitors.
Keywords:Clostridium perfringens  DEG  Essential genes  Drug targets  Broad-spectrum anti microbial drug
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