Aim: Nontuberculous mycobacterial (NTM) infection such as endophthalmitis, dacryocystitis, and canaliculitis are pervasive across the globe and are currently managed by antibiotics. However, the recent cases of Mycobacteroides developing drug resistance reported along with the improper practice of medicine intrigued us to explore its genomic and proteomic canvas at a global scale and develop a chimeric vaccine against Mycobacteroides.
Main methods: We carried out a vivid genomic study on five recently sequenced strains of Mycobacteroides and explored their Pan-core genome/proteome in three different phases. The promiscuous antigenic proteins were identified via a subtractive proteomics approach that qualified for virulence causation, resistance and essentiality factors for this notorious bacterium. An integrated pipeline was developed for the identification of B-Cell, MHC (Major histocompatibility complex) class I and II epitopes.
Key findings: Phase I identified the shreds of evidence of reductive evolution and propensity of the Pan-genome of Mycobacteroides getting closed soon. Phase II and Phase III produced 8 vaccine constructs. Our final vaccine construct, V6 qualified for all tests such as absence for allergenicity, presence of antigenicity, etc. V6 contains β-defensin as an adjuvant, linkers, Lysosomal-associated membrane protein 1 (LAMP1) signal peptide, and PADRE (Pan HLA-DR epitopes) amino acid sequence. Besides, V6 also interacts with a maximum number of MHC molecules and the TLR4/MD2 (Toll-like receptor 4/Myeloid differentiation factor 2) complex confirmed by docking and molecular dynamics simulation studies.
Significance: The knowledge harnessed from the current study can help improve the current treatment regimens or in an event of an outbreak and propel further related studies.
Keywords: Chimeric-subunit vaccine; Mycobacteroides; Nontuberculous mycobacterial (NTM) infection; Pan-core; TLR4/MD2.
Copyright © 2020 Elsevier Inc. All rights reserved.