Abstract
Background 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.ConclusionsThe 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.
Highlights
Mycobacterium leprae and Mycobacterium lepromatosis are gram-positive bacterial pathogens and the causative agents of leprosy in humans across the world
Until 2008, the only organism known for causing leprosy was Mycobacterium leprae, but a new species was identified as the causative agent of diffuse lepromatous leprosy (DLL)
Comparative genomics approach was carried out in order to cluster orthologous genes to get a framework to incorporate information from multiple genomes, highlighting the conservation and divergence of gene families and biological processes; for pathogens clustering, orthologs can simplify the identification of drug and/or vaccine targets
Summary
Mycobacterium leprae and Mycobacterium lepromatosis are gram-positive bacterial pathogens and the causative agents of leprosy in humans across the world. The newly identified species was Mycobacterium lepromatosis, obtained from the blood sample of two patients of Mexican origin who passed away because of the disease and identified as a causative agent for atypical leprosy [1,2,3]. This disease may occur at any age, mostly affects the skin, peripheral nerves, mucosal surface of the upper respiratory tract and eyes [4, 5]. These places represent almost 14% of the Brazilian population [11, 12]
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