title: Proteome mining for the identification and in-silico characterization of putative drug targets of multi-drug resistant Clostridium difficile strain 630.
abstract: Clostridium difficile is an enteric pathogen that causes approximately 20% to 30% of antibiotic-associated diarrhea. In recent years, there has been a substantial rise in the rate of C. difficile infections as well as the emergence of virulent and antibiotic resistant C. difficile strains. So, there is an urgent need for the identification of therapeutic potential targets and development of new drugs for the treatment and prevention of C. difficile infections. In the current study, we used a hybrid approach by combining sequence similarity-based approach and protein-protein interaction network topology-based approach to identify and characterize the potential drug targets of C. difficile. A total of 155 putative drug targets of C. difficile were identified and the metabolic pathway analysis of these putative drug targets using DAVID revealed that 46 of them are involved in 9 metabolic pathways. In-silico characterization of these proteins identified seven proteins involved in pathogen-specific peptidoglycan biosynthesis pathway. Three promising targets viz. homoserine dehydrogenase, aspartate-semialdehyde dehydrogenase and aspartokinase etc. were found to be involved in multiple enzymatic pathways of the pathogen. These 3 drug targets are of particular interest as they can be used for developing effective drugs against multi-drug resistant C. difficile strain 630 in the near future.
authors.affiliation: Department of Biosciences, Integral University, Lucknow, India; Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia. Electronic address: mlohani@jazanu.edu.sa.
authors.forename: Mohtashim
authors.initials: M
authors.lastname: Lohani
authors.affiliation: Department of Biotechnology, Amity University, Lucknow, India.
authors.forename: Anupam
authors.initials: A
authors.lastname: Dhasmana
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.
authors.forename: Shafiul
authors.initials: S
authors.lastname: Haque
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.
authors.forename: Mohd
authors.initials: M
authors.lastname: Wahid
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.
authors.forename: Arshad
authors.initials: A
authors.lastname: Jawed
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.
authors.forename: Sajad A
authors.initials: SA
authors.lastname: Dar
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.
authors.forename: Raju K
authors.initials: RK
authors.lastname: Mandal
authors.affiliation: Research and Scientific Studies Unit, College of Nursing and Allied Health Sciences, Jazan University, Jazan, Saudi Arabia.
authors.forename: Mohammed Y
authors.initials: MY
authors.lastname: Areeshi
authors.affiliation: College of Applied Medical Sciences, Hail University, Hail, Saudi Arabia.
authors.forename: Saif
authors.initials: S
authors.lastname: Khan
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001222:Aspartate Kinase; D001223:Aspartate-Semialdehyde Dehydrogenase / Q000378:metabolism; D001426:Bacterial Proteins / Q000187:drug effects / Q000302:isolation & purification* / Q000378:metabolism; D001669:Biochemical Phenomena; D016360:Clostridioides difficile / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods*; D016503:Drug Delivery Systems / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D018432:Drug Resistance, Multiple; D004761:Enterocolitis, Pseudomembranous / Q000188:drug therapy; D020043:Genes, Essential / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics / Q000502:physiology; D008954:Models, Biological; D010457:Peptidoglycan / Q000096:biosynthesis / Q000378:metabolism; D054730:Protein Interaction Domains and Motifs; D020543:Proteome / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D010457:Peptidoglycan; D020543:Proteome; D001223:Aspartate-Semialdehyde Dehydrogenase; D001222:Aspartate Kinase
keywords: Clostridium difficile; Essential protein; Protein-protein interaction; Target identification