In-silico Subtractive Proteomic Analysis Approach for Therapeutic Targets in MDR Salmonella enterica subsp. enterica serovar Typhi str. CT18

Author(s): Noor Rahman, Ijaz Muhammad, Gul E. Nayab, Haroon Khan*, Rosanna Filosa, Jianbo Xiao, Sherif T.S. Hassan.

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 29 , 2019

DOI : 10.2174/1568026619666191105102156

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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.

Keywords: Salmonellosis, Therapeutic target, Multi-drug-resistance, Database of essential genes, Druggability, Proteomic.

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VOLUME: 19
ISSUE: 29
Year: 2019
Page: [2708 - 2717]
Pages: 10
DOI: 10.2174/1568026619666191105102156
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