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.

中文翻译：

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针对针对多种分枝杆菌的嵌合疫苗-一种综合方法。

AIM非结核性分枝杆菌（NTM）感染，例如眼内炎，泪囊炎和细小管炎遍布全球，目前由抗生素控制。然而，最近报道的分支杆菌产生耐药性的案例以及不正确的医学实践引起了我们的兴趣，以在全球范围内探索其基因组和蛋白质组学，并开发了针对分支杆菌的嵌合疫苗。主要方法我们对五个最近测序的分枝杆菌菌株进行了生动的基因组研究，并在三个不同阶段探索了它们的Pan-core基因组/蛋白质组。通过消减蛋白质组学方法鉴定了混杂抗原蛋白，该方法符合该臭名昭著细菌的毒力原因，抗性和必需因子。开发了一条集成管线，用于鉴定B细胞，MHC（主要组织相容性复合体）I类和II类表位。主要发现第一阶段发现了分支杆菌的全基因组即将关闭的还原性进化和倾向的证据。II期和III期产生了8种疫苗构建体。我们最终的疫苗构建体V6可通过所有测试，例如无变应原性，是否存在抗原性等。V6包含β-防御素作为佐剂，接头，溶酶体相关膜蛋白1（LAMP1）信号肽和PADRE（Pan HLA） -DR表位）氨基酸序列。此外，通过对接和分子动力学模拟研究证实，V6还与最大数量的MHC分子和TLR4 / MD2（Toll样受体4 /骨髓分化因子2）复合物相互作用。