Finding Potential Therapeutic Targets against Shigella flexneri through Proteome Exploration.

Mohammad Uzzal Hossain,Md Monirul Islam,Mohammad Neaz Morshed,Md Arif Khan,Md Salimullah,Chaman Ara Keya,Abu Hashem

doi:10.3389/fmicb.2016.01817

Mohammad Uzzal Hossain, Md Monirul Islam + Show 5 more

Open Access

https://doi.org/10.3389/fmicb.2016.01817

Copy DOI

Abstract

Background: Shigella flexneri is a gram negative bacteria that causes the infectious disease “shigellosis.” S. flexneri is responsible for developing diarrhea, fever, and stomach cramps in human. Antibiotics are mostly given to patients infected with shigella. Resistance to antibiotics can hinder its treatment significantly. Upon identification of essential therapeutic targets, vaccine and drug could be effective therapy for the treatment of shigellosis.Methods: The study was designed for the identification and qualitative characterization for potential drug targets from S. flexneri by using the subtractive proteome analysis. A set of computational tools were used to identify essential proteins those are required for the survival of S. flexneri. Total proteome (13,503 proteins) of S. flexneri was retrieved from NCBI and further analyzed by subtractive channel analysis. After identification of the metabolic proteins we have also performed its qualitative characterization to pave the way for the identification of promising drug targets.Results: Subtractive analysis revealed that a list of 53 targets of S. flexneri were human non-homologous essential metabolic proteins that might be used for potential drug targets. We have also found that 11 drug targets are involved in unique pathway. Most of these proteins are cytoplasmic, can be used as broad spectrum drug targets, can interact with other proteins and show the druggable properties. The functionality and drug binding site analysis suggest a promising effective way to design the new drugs against S. flexneri.Conclusion: Among the 53 therapeutic targets identified through this study, 13 were found highly potential as drug targets based on their physicochemical properties whilst only one was found as vaccine target against S. flexneri. The outcome might also be used as module as well as circuit design in systems biology.

Highlights

In developing countries, S. flexnari is the foremost reason of bacillary dysentery among the four species of Shigella
An in silico systematic method consists of three stages is applied to classify and illustrate possible drug targets against S. flexneri
The strategy applied a hierarchy of subtractive analysis where functionally essential proteins of S. flexneri derived from whole proteome of 13,503 proteins dataset (Drug Target, Data Sheet S1)

Summary

Introduction

S. flexnari is the foremost reason of bacillary dysentery among the four species of Shigella. As Gram-negative facultative human pathogens, cause intestinal infections with sign and symptoms such as fever, abdominal cramps and watery, or bloody diarrhea. Majority of endemic dysentery are caused by S. flexneri in regions of the world having less facility of sanitation. It has been reported that Shigella serotypes including S. flexneri 2a, 3a, S. dysenteriae 1, and S. sonnei are targeted for vaccine development. The first three are more widespread while the last serotypes found in regions where sanitation standard is high (Jennison and Verma, 2004; Mukhopadhaya et al, 2006). Shigella flexneri is a gram negative bacteria that causes the infectious disease “shigellosis.” S. flexneri is responsible for developing diarrhea, fever, and stomach cramps in human. Resistance to antibiotics can hinder its treatment significantly. Upon identification of essential therapeutic targets, vaccine and drug could be effective therapy for the treatment of shigellosis

Methods

Results

Conclusion