Reverse vaccinology and subtractive genomics approaches for identifying common therapeutics against Mycobacterium leprae and Mycobacterium lepromatosis

Mycobacterium leprae and Mycobacterium lepromatosis are gram-positive bacterial pathogens and the causative agents of leprosy in humans across the world. The elimination of leprosy cannot be achieved by multidrug therapy alone, and highlights the need for new tools and drugs to prevent the emergence of new resistant strains. Methods In this study, our contribution includes the prediction of vaccine targets and new putative drugs against leprosy, using reverse vaccinology and subtractive genomics. Six strains of Mycobacterium leprae and Mycobacterium lepromatosis (4 and 2 strains, respectively) were used for comparison taking Mycobacterium leprae strain TN as the reference genome. Briefly, we used a combined reverse vaccinology and subtractive genomics approach. Results As a result, we identified 12 common putative antigenic proteins as vaccine targets and three common drug targets against Mycobacterium leprae and Mycobacterium lepromatosis. Furthermore, the docking analysis using 28 natural compounds with three drug targets was done. Conclusions The bis-naphthoquinone compound Diospyrin (CID 308140) obtained from indigenous plant Diospyros spp. showed the most favored binding affinity against predicted drug targets, which can be a candidate therapeutic target in the future against leprosy.(AU)

Complemento, daño renal y lepra murina / Complement, renal damage and murine leprosy

A pesar de que la lepra de los ratones es una enfermedad sistémica, el tejido renal de los animales infectados rara vez es invadido por el Mycobacterium lepraemurium. Nuestros resultados indicaron que los animales afectados con el Mycobacterium lepraemurium desarrollaron un defecto en sus niveles de complemento hemolítico que es proporcional al grado de infección. El defecto afecta principalmente la vía clásica de activación del complemento y menor marcadamente la vía alterna. La inactivación de la actividad de complemento, mientras transcurre la infección, disminuye la posibilidad del daño medido por completo y prolonga la vida del huésped murino; ésta es, sin duda, una eficiente estrategia del microorganismo para prolongar también su supervivencia