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

TITLE=Finding Potential Therapeutic Targets against Shigella flexneri through Proteome Exploration

JOURNAL=Frontiers in Microbiology

VOLUME=7

YEAR=2016

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.01817

DOI=10.3389/fmicb.2016.01817

ISSN=1664-302X

ABSTRACT=<p><bold>Background:</bold><italic>Shigella flexneri</italic> is a gram negative bacteria that causes the infectious disease “shigellosis.” <italic>S. flexneri</italic> 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.</p><p><bold>Methods:</bold> The study was designed for the identification and qualitative characterization for potential drug targets from <italic>S. flexneri</italic> by using the subtractive proteome analysis. A set of computational tools were used to identify essential proteins those are required for the survival of <italic>S. flexneri</italic>. Total proteome (13,503 proteins) of <italic>S. flexneri</italic> 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.</p><p><bold>Results:</bold> Subtractive analysis revealed that a list of 53 targets of <italic>S. flexneri</italic> 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 <italic>S. flexneri</italic>.</p><p><bold>Conclusion:</bold> 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 <italic>S. flexneri</italic>. The outcome might also be used as module as well as circuit design in systems biology.</p>