Mitochondrial variants of complex I genes associated with leprosy clinical subtypes

• Published in: Scientific reports 2024-03, Vol.14 (1), p.6365-6365, Article 6365
• Main Authors: de Souza, Felipe Gouvea, Silva, Caio S., de Araújo, Gilderlanio S., Santana-da-Silva, Mayara N., Gobbo, Angélica Rita, da Silva, Moisés Batista, Pinto, Pablo, da Costa, Patrícia Fagundes, Salgado, Claudio Guedes, Ribeiro-dos-Santos, Ândrea, Cavalcante, Giovanna C.
• Format: Article
• Language: English
• Subjects: 631/208/212/2301; 631/250/255; Antigens, Bacterial; Bacterial diseases; Bacterial infections; Chronic infection; Complex I; DNA, Mitochondrial; Electron transport chain; Heteroplasmy; Humanities and Social Sciences; Humans; Leprosy; Leprosy - genetics; Mitochondria; Mitochondrial DNA; mtDNA; multidisciplinary; Mutation; Mycobacterium leprae - genetics; Oxidative phosphorylation; Pathogenicity; Pathogens; Peripheral nerves; Phosphorylation; Science; Science (multidisciplinary); Skin
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-57191-y

Leprosy is a chronic bacterial infection mainly caused by Mycobacterium leprae that primarily affects skin and peripheral nerves. Due to its ability to absorb carbon from the host cell, the bacillus became dependent on energy production, mainly through oxidative phosphorylation. In fact, variations in genes of Complex I of oxidative phosphorylation encoded by mtDNA have been associated with several diseases in humans, including bacterial infections, which are possible influencers in the host response to leprosy. Here, we investigated the presence of variants in the mtDNA genes encoding Complex I regarding leprosy, as well as the analysis of their pathogenicity in the studied cohort. We found an association of 74 mitochondrial variants with either of the polar forms, Pole T (Borderline Tuberculoid) or Pole L (Borderline Lepromatous and Lepromatous) of leprosy. Notably, six variants were exclusively found in both clinical poles of leprosy, including m.4158A>G and m.4248T>C in MT-ND1 , m.13650C>A, m.13674T>C, m.12705C>T and m.13263A>G in MT-ND5, of which there are no previous reports in the global literature. Our observations reveal a substantial number of mutations among different groups of leprosy, highlighting a diverse range of consequences associated with mutations in genes across these groups. Furthermore, we suggest that the six specific variants exclusively identified in the case group could potentially play a crucial role in leprosy susceptibility and its clinical differentiation. These variants are believed to contribute to the instability and dysregulation of oxidative phosphorylation during the infection, further emphasizing their significance.