Title:In-silico Subtractive Proteomic Analysis Approach for Therapeutic Targets in MDR Salmonella enterica subsp. enterica serovar Typhi str. CT18
VOLUME: 19 ISSUE: 29
Author(s):Noor Rahman, Ijaz Muhammad, Gul E. Nayab, Haroon Khan*, Rosanna Filosa, Jianbo Xiao and Sherif T.S. Hassan
Affiliation:Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan-23200, KP, Department of Zoology, Abdul Wali Khan University Mardan, Mardan-23200, KP, Department of Zoology, Abdul Wali Khan University Mardan, Mardan-23200, KP, Department of Pharmacy, Abdul Wali Khan University Mardan, Mardan-23200, KP, Università della Campania Luigi Vanvitelli, Department of Environmental Biological and Pharmaceutical Sciences and Technologies, Naples, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Control in Chinese Medicine, University of Macau, Taipa, Department of Natural Drugs, Faculty of Pharmacy, University of Veterinary and Pharmaceutical Sciences Brno, Brno
Keywords:Salmonellosis, Therapeutic target, Multi-drug-resistance, Database of essential genes, Druggability, Proteomic.
Abstract:
Objective: In the present study, an attempt has been made for subtractive proteomic analysis
approach for novel drug targets in Salmonella enterica subsp. enterica serover Typhi str.CT18 using
computational tools.
Methods: Paralogous, redundant and less than 100 amino acid protein sequences were removed by using
CD-HIT. Further detection of bacterial proteins which are non-homologous to host and are essential for
the survival of pathogens by using BLASTp against host proteome and DEG`s, respectively. Comparative
Metabolic pathways analysis was performed to find unique and common metabolic pathways. The
non-redundant, non-homologous and essential proteins were BLAST against approved drug targets for
drug targets while Psortb and CELLO were used to predict subcellular localization.
Results: There were 4473 protein sequences present in NCBI Database for Salmonella enterica subsp.
enterica serover Typhi str. CT18 out of these 327 were essential proteins which were non-homologous
to human. Among these essential proteins, 124 proteins were involved in 19 unique metabolic pathways.
These proteins were further BLAST against approved drug targets in which 7 cytoplasmic proteins
showed druggability and can be used as a therapeutic target.
Conclusion: Drug targets identification is the prime step towards drug discovery. We identified 7 cytoplasmic
druggable proteins which are essential for the pathogen survival and non-homologous to human
proteome. Further in vitro and in vivo validation is needed for the evaluation of these targets to combat
against salmonellosis.