Subtractive proteomics to identify novel drug targets and reverse vaccinology for the development of chimeric vaccine against Acinetobacter baumannii

Vandana Solanki,Vishvanath Tiwari

doi:10.1038/s41598-018-26689-7

Vandana Solanki, Vishvanath Tiwari

Open Access

https://doi.org/10.1038/s41598-018-26689-7

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Journal: Scientific Reports	Publication Date: Jun 13, 2018
Citations: 184	License type: open-access

Affiliation: Central University of Rajasthan

Abstract

The emergence of drug-resistant Acinetobacter baumannii is the global health problem associated with high mortality and morbidity. Therefore it is high time to find a suitable therapeutics for this pathogen. In the present study, subtractive proteomics along with reverse vaccinology approaches were used to predict suitable therapeutics against A. baumannii. Using subtractive proteomics, we have identified promiscuous antigenic membrane proteins that contain the virulence factors, resistance factors and essentiality factor for this pathogenic bacteria. Selected promiscuous targeted membrane proteins were used for the design of chimeric-subunit vaccine with the help of reverse vaccinology. Available best tools and servers were used for the identification of MHC class I, II and B cell epitopes. All selected epitopes were further shortlisted computationally to know their immunogenicity, antigenicity, allergenicity, conservancy and toxicity potentials. Immunogenic predicted promiscuous peptides used for the development of chimeric subunit vaccine with immune-modulating adjuvants, linkers, and PADRE (Pan HLA-DR epitopes) amino acid sequence. Designed vaccine construct V4 also interact with the MHC, and TLR4/MD2 complex as confirm by docking and molecular dynamics simulation studies. Therefore designed vaccine construct V4 can be developed to control the host-pathogen interaction or infection caused by A. baumannii.

Highlights

Acinetobacter baumannii, an ESKAPE pathogen, has gained the attention of medical fraternity worldwide due to its nosocomial infection in hospital setup mainly ICUs and emergence of multi-drug resistance mechanism in it[1,2,3,4,5,6]
Previous studies reveal that outer membrane proteins OmpA, biofilm-associated protein, poly-N-acetyl-β-(1– 6)-glucosamine[8], trimeric autotransporter protein, K1 capsular polysaccharide, outer membrane vesicles (OMV) and formalin-inactivated whole cells could serve as vaccine candidates and provide partial immunity against lethal doses in various mouse models[9]
All the 1578 strains of A. baumannii were manually separated according to their redundancy and non-redundancy

Summary

Introduction

Acinetobacter baumannii, an ESKAPE pathogen, has gained the attention of medical fraternity worldwide due to its nosocomial infection in hospital setup mainly ICUs and emergence of multi-drug resistance mechanism in it[1,2,3,4,5,6]. It is shown that subtractive genomics and reverse vaccinology as a powerful tool to identify drug target and vaccine candidates. Subtractive genomics approach subtracts pathogen genes that are required the survival of pathogen but not present in the host[13] This is important to find druggable protein, which may be considered for the therapeutics development. The selected druggable proteins may be used for the development of the chimeric-subunit vaccine or multi-subunit vaccine that appears as a very promising and effective treatment option to control the diseases caused by this pathogen[14]. Once shortlisted, these candidates can be cloned and over-expressed in E. coli and purified by affinity chromatography. The designed chimeric-subunit vaccine can be developed to cure the infection caused by the A. baumannii

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Conclusion