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Toward a chimeric vaccine against multiple isolates of Mycobacteroides - An integrative approach.
Life Sci. 2020 Jun 01; 250:117541.LS

Abstract

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.

Authors+Show Affiliations

Department of Biotechnology, Noida Institute of Engineering and Technology (NIET), Greater Noida, India.Institute of Clinical Medicine, University of Eastern Finland, Kuopio Campus, Finland.Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida, India. Electronic address: niraj.jha@sharda.ac.in.Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida, India.Department of Biotechnology, School of Engineering & Technology (SET), Sharda University, Greater Noida, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32169520

Citation

Satyam, Rohit, et al. "Toward a Chimeric Vaccine Against Multiple Isolates of Mycobacteroides - an Integrative Approach." Life Sciences, vol. 250, 2020, p. 117541.
Satyam R, Bhardwaj T, Jha NK, et al. Toward a chimeric vaccine against multiple isolates of Mycobacteroides - An integrative approach. Life Sci. 2020;250:117541.
Satyam, R., Bhardwaj, T., Jha, N. K., Jha, S. K., & Nand, P. (2020). Toward a chimeric vaccine against multiple isolates of Mycobacteroides - An integrative approach. Life Sciences, 250, 117541. https://doi.org/10.1016/j.lfs.2020.117541
Satyam R, et al. Toward a Chimeric Vaccine Against Multiple Isolates of Mycobacteroides - an Integrative Approach. Life Sci. 2020 Jun 1;250:117541. PubMed PMID: 32169520.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Toward a chimeric vaccine against multiple isolates of Mycobacteroides - An integrative approach. AU - Satyam,Rohit, AU - Bhardwaj,Tulika, AU - Jha,Niraj Kumar, AU - Jha,Saurabh Kumar, AU - Nand,Parma, Y1 - 2020/03/10/ PY - 2020/01/20/received PY - 2020/03/07/revised PY - 2020/03/08/accepted PY - 2020/3/15/pubmed PY - 2020/5/6/medline PY - 2020/3/15/entrez KW - Chimeric-subunit vaccine KW - Mycobacteroides KW - Nontuberculous mycobacterial (NTM) infection KW - Pan-core KW - TLR4/MD2 SP - 117541 EP - 117541 JF - Life sciences JO - Life Sci. VL - 250 N2 - 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. SN - 1879-0631 UR - https://www.unboundmedicine.com/medline/citation/32169520/Toward_a_chimeric_vaccine_against_multiple_isolates_of_Mycobacteroides_-_An_integrative_approach L2 - https://linkinghub.elsevier.com/retrieve/pii/S0024-3205(20)30289-7 DB - PRIME DP - Unbound Medicine ER -