Abstract
BackgroundMycobacterium tuberculosis (Mtb) is an etiological agent of tuberculosis (TB). Tuberculosis is a mounting problem worldwide. The only available vaccine BCG protects the childhood but not adulthood form of TB. Therefore, efforts are made continuously to improve the efficacy of BCG by supplementing it with other therapies. Consequently, we explored the possibility of employing Mycobacterium immunogenum (Mi) to improve BCG potential to protect against Mtb.ResultsWe report here the genome mining, comparative genomics, immunological and protection studies employing strain CD11_6 of Mi. Mycobacterium immunogenum was isolated from duodenal mucosa of a celiac disease patient. The strain was whole genome sequenced and annotated for identification of virulent genes and other traits that may make it suitable as a potential vaccine candidate. Virulence profile of Mi was mapped and compared with two other reference genomes i.e. virulent Mtb strain H37Rv and vaccine strain Mycobacterium bovis (Mb) AFF2122/97. This comparative analysis revealed that Mi is less virulent, as compared to Mb and Mtb, and contains comparable number of genes encoding for the antigenic proteins that predict it as a probable vaccine candidate. Interestingly, the animals vaccinated with Mi showed significant augmentation in the generation of memory T cells and reduction in the Mtb burden.ConclusionThe study signifies that Mi has a potential to protect against Mtb and therefore can be a future vaccine candidate against TB.
Highlights
Mycobacterium tuberculosis (Mtb) is an etiological agent of tuberculosis (TB)
Characterization and phylogenetic analysis of strain CD11_6 The Mycobacterium immunogenum (Mi) strain designated as CD11_6 had matched with most of the phenotypic (Gram-positive, aerobic, rods in shape, acid fast, non-motile) characteristics of the genus Mycobacterium and most of the other features matched with the species M. immunogenum (Mi): negative for nitrate reduction, utilization of citrate; positive for D-glucitol, i-myo-inositol, and D-mannitol
Using genome mining and annotation results, we depicted the presence of similar genes in Mi encoding for surface membrane antigens, membrane transport and cytosolic proteins as of Mtb
Summary
Mycobacterium tuberculosis (Mtb) is an etiological agent of tuberculosis (TB). Tuberculosis is a mounting problem worldwide. Prior published literature suggests a probable role of Mi in eliciting immune response [15, 16] This preliminary information had derived our interest to explore protective efficacy of Mi against Mtb. Keeping in view of above mentioned facts, we adjudged to use heat killed Mi as a vaccine candidate and check its efficacy against Mtb. The present study indicates that Mi can induce optimum activation of both CD4 T cells and CD8 T cells. Enhancement in the pool of memory T cells was noticed, as indicated by modulation in the expression of the memory markers CD44, CD127 and CD62L This signifies a possible use of Mi as a vaccine candidate against Mtb
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