Combating tigecycline resistant Acinetobacter baumannii: A leap forward towards multiple-epitope based vaccine discovery

Sajjad Ahmad, Kara Ranaghan, Syed Sikander Azam*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

12 Citations (Scopus)
84 Downloads (Pure)

Abstract

Global emergence of Tigecycline resistant Acinetobacter baumannii (TRAB) is on the horizon and poses a very serious threat to human health. There is a pressing demand for suitable therapeutics against this pathogen, particularly a vaccine to protect against TRAB infections. We present a comprehensive investigation of the complete proteome of a TRAB AB031 strain to predict promiscuous antigenic, non-allergenic, virulent B-cell derived T-cell epitopes and formulate a multi-epitope vaccine against the pathogen. We identified epitopes from three proteins: outer membrane protein assembly factor (BamA), fimbrial biogenesis outer membrane usher protein (FimD) and type IV secretion protein (Rhs) that are appropriate for vaccine design. These proteins constitute the core proteome of the pathogen, are essential, localized at the pathogen surface, non-homologous to humans, mice and to the beneficial probiotic bacteria that reside the human gut. Moreover, these proteins are ideal candidates for experimental investigation as they have favorable physicochemical properties and have strong cellular interacting networks. The predicted epitopes: FPLNDKPGD (BamA), FVHAEEAAA (FimD) and YVVAGTAAA (Rhs) have exo-membrane topology for efficient recognition of the host immune system and high affinity for the most prevalent allele in human populations, the DRB*0101. These epitopes were linked and attached to an adjuvant to enhance its antigenicity. The multi-epitope vaccine-construct was docked with the TLR4 receptor to assess its affinity for the protein and thus its presentation to the host immune system. Docking results were validated through molecular dynamics simulations and binding free energies were calculated using the molecular mechanics/generalized Born (MM-GBSA) method. In conclusion, we expect the designed chimeric vaccine is highly likely to be effective against infections caused by TRAB.

Original languageEnglish
Pages (from-to)1-17
Number of pages17
JournalEuropean Journal of Pharmaceutical Sciences
Volume132
Early online date21 Feb 2019
DOIs
Publication statusPublished - 30 Apr 2019

Keywords

  • Tigecycline resistant Acinetobacter baumannii
  • vaccine
  • b-cell deprived T-cell epitopes
  • molecular docking
  • molecular dynamics simulation

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