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

Authors :
Tiago Araujo Gomes
Tatiana Pereira da Silva
Edson Machado
Sidra Ezidio Gonçalves Vasconcelos
Bruno Siqueira Mietto
Daniela Ferreira de Faria Bertoluci
Patricia Sammarco Rosa
Roberta Olmo Pinheiro
Philip Noel Suffys
Letícia Miranda Santos Lery
Flavio Alves Lara
Source :
Pathogens, Vol 13, Iss 11, p 986 (2024)
Publication Year :
2024
Publisher :
MDPI AG, 2024.

Abstract

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.

Details

Language :
English
ISSN :
20760817
Volume :
13
Issue :
11
Database :
Directory of Open Access Journals
Journal :
Pathogens
Publication Type :
Academic Journal
Accession number :
edsdoj.fc976f82b1ce4c03bdc105b60aa1e32e
Document Type :
article
Full Text :
https://doi.org/10.3390/pathogens13110986