Insights Into The Structure And Dynamics Of Shigella Invasion Proteins For Use As Potential Drug Targets

Abstract

The Gram-negative bacteria, Shigella spp. has always been a pathogen of concern in the context of global burden of diarrheal diseases, with recent surveys taking the annual incidence of shigellosis to roughly 125 million cases worldwide. The scenario has been further worsened by the frequent reports on isolation of multi drug resistant (MDR) Shigella strains, showing resistance against potent antibiotics including the 3rd generation cephalosporins as well. With the recent years witnessing a growing interest in the discovery of novel drugs, this work has scrutinized the structural nitty-gritty of the predominant virulence factors in Shigella, viz. the invasion plasmid antigens IpaA, IpaB, IpaC and IpaD, that are evidenced to have multifaceted role in the pathogenesis cascade, to explore their potential as promising therapeutic targets. In this work we report the 3D models of the different invasion proteins using comparative modeling and a comprehensive structural evaluation protocol for evaluating their stability as drug targets. Our data suggest significant potential of these invasion proteins to serve as future drug targets, thus opening up the avenue for further investigations.