Abstract
Shigellosis is characterized as diarrheal disease that causes a high mortality rate especially in children, elderly and immunocompromised patients. More recently, the World Health Organization advised safe vaccine designing against shigellosis due to the emergence of Shigella dysenteriae resistant strains. Therefore, the aim of this study is to identify novel drug targets as well as the design of the potential vaccine candidates and chimeric vaccine models against Shigella dysenteriae. A computational based Reverse Vaccinology along with subtractive genomics analysis is one of the robust approaches used for the prioritization of drug targets and vaccine candidates through direct screening of genome sequence assemblies. Herein, a successfully designed peptide-based novel highly antigenic chimeric vaccine candidate against Shigella dysenteriae sd197 strain is proposed. The study resulted in six epitopes from outer membrane WP_000188255.1 (Fe (3+) dicitrate transport protein FecA) that ultimately leads to the construction of twelve vaccine models. Moreover, V9 construct was found to be highly immunogenic, non-toxic, non-allergenic, highly antigenic, and most stable in terms of molecular docking and simulation studies against six HLAs and TLRS/MD complex. So far, this protein and multiepitope have never been characterized as vaccine targets against Shigella dysenteriae. The current study proposed that V9 could be a significant vaccine candidate against shigellosis and to ascertain that further experiments may be applied by the scientific community focused on shigellosis.
Highlights
Shigella spp. is a facultative anaerobic, non-motile, and gram-negative bacterium that causes severe diarrhea and dysenteric disease called shigellosis or bacillary d ysentery[1]
Subtractive genomics plays a pivotal role in novel drug target identification which is unique and essential for the survival of the pathogen without altering the host biochemical pathways
The current study identified 77 proteins as essential, virulent, druggable, and cytoplasmic proteins that may act as potent drug targets against S. dysenteriae, while one protein was classified as outer membrane i.e. WP_000188255.1 (Fe (3+) dicitrate transport protein FecA)
Summary
Shigella spp. is a facultative anaerobic, non-motile, and gram-negative bacterium that causes severe diarrhea and dysenteric disease called shigellosis or bacillary d ysentery[1]. The infection mechanism of Shigella spp begins with the binding and entrance into the epithelial cell of the intestine with the help of exposed needle like structure known as type three secretory system (T3SS) formed by Spa and Mxi proteins. Evidence revealed that the attenuated bacterial vaccines may have the ability to stimulate immune system and previously used against Shigella dysenteriae[8]. All those vaccines have shown limitations due to instability, limited protection period, and r eactogenicity[9]. Computational based method typically utilizes alternate approaches for finding novel drug targets and designing multi-epitopes vaccines, designing structure-based drugs, elucidating the host–pathogen interactions, allowing genome-based comparative study, and so on thereby reducing the conventional laboratory-based experimental p ractices[11]. There is an urgent need to identify novel drug targets and find a new and reliable vaccine model to fight against shigellosis
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