Genomic and Phenotypic Variations Among Thai-53 and Mycobacterium leprae Clinical Isolates: Implications for Leprosy Pathogenesis and Research.

Autor:	Gomes TA; Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.; Rede de Micobactérias, Programa Inova-IOC, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil., da Silva TP; Rede de Micobactérias, Programa Inova-IOC, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.; Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil., Machado E; Rede de Micobactérias, Programa Inova-IOC, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.; Laboratório de Biologia Molecular Aplicada a Micobactérias, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil., Vasconcelos SEG; Rede de Micobactérias, Programa Inova-IOC, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.; Laboratório de Biologia Molecular Aplicada a Micobactérias, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil., Mietto BS; Laboratório de Neurobiologia, Instituto de Ciências Biológicas, Universidade de Juiz de Fora, Juiz de Fora 36036-900, Brazil., de Faria Bertoluci DF; Divisão de Pesquisa e Ensino, Instituto Lauro de Souza Lima, Bauru 17034-971, Brazil., Rosa PS; Divisão de Pesquisa e Ensino, Instituto Lauro de Souza Lima, Bauru 17034-971, Brazil., Pinheiro RO; Rede de Micobactérias, Programa Inova-IOC, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.; Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil., Suffys PN; Rede de Micobactérias, Programa Inova-IOC, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.; Laboratório de Biologia Molecular Aplicada a Micobactérias, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil., Lery LMS; Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil., Lara FA; Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.; Rede de Micobactérias, Programa Inova-IOC, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil.
Jazyk:	angličtina
Zdroj:	Pathogens (Basel, Switzerland) [Pathogens] 2024 Nov 12; Vol. 13 (11). Date of Electronic Publication: 2024 Nov 12.
DOI:	10.3390/pathogens13110986
Abstrakt:	Throughout Mycobacterium leprae's ( M. leprae ) evolutionary trajectory, nearly half of its genome was converted into pseudogenes. Despite this drastic reduction in genetic content, the genome sequence identity among M. leprae isolates worldwide is remarkably high compared to other pathogens. In this study, we investigated the genotype and morphotype of three M. leprae strains: the reference strain Thai-53 (genotype 1A), and two clinical isolates from Brazilian leprosy relapse patients, which were Br014-03 (genotypes 3I) and Br014-01(4N). We compared their genome sequences and their interaction with human Schwann cells from the ST88-14 lineage and with human primary macrophages. On the genetic level, we observed over a hundred missense mutations in the three strains, translated into significant phenotypic changes such as: prolonged doubling time, altered cytokine induction, reduced interaction rates, and decreased intracellular viability in Schwann cells. Our findings underscore the concept that despite their 99.992% identity, even small genomic disparities in M. leprae genomes can elicit substantial alterations in bacilli interaction with host cells and subsequent immune responses. Consequently, our data could lead to better comprehension of correlation between pathogen mutations and the diverse clinical manifestations observed in leprosy patients.
Databáze:	MEDLINE
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