02429nas a2200349   4500000000100000008004100001260001200042653001300054653001300067653000900080653001200089653001200101653002900113653003300142100001200175700001500187700001400202700001800216700001300234700001600247700001100263700001500274700001300289700001100302700001100313245014800324856012400472300000900596490000700605520145300612022001402065       2024                            d  c11/202410aBr014-0110aBr014-0310aSNPs10aThai-5310aleprosy10anon-synonymous mutations10asingle nucleotide polymorphs1 aGomes T1 ada Silva T1 aMachado E1 aVasconcelos S1 aMietto B1 aBertoluci D1 aRosa P1 aPinheiro R1 aSuffys P1 aLery L1 aLara F00aGenomic and Phenotypic Variations Among Thai-53 and Mycobacterium leprae Clinical Isolates: Implications for Leprosy Pathogenesis and Research.  uhttps://mdpi-res.com/d_attachment/pathogens/pathogens-13-00986/article_deploy/pathogens-13-00986.pdf?version=1731375388  a1-170 v133 a<p>Throughout <em>Mycobacterium leprae's</em>&nbsp;(<em>M. leprae</em>) evolutionary trajectory, nearly half of its genome was converted into pseudogenes. Despite this drastic reduction in genetic content, the genome sequence identity among&nbsp;<em>M. leprae</em>&nbsp;isolates worldwide is remarkably high compared to other pathogens. In this study, we investigated the genotype and morphotype of three <em>M. leprae</em>&nbsp;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 <em>M. leprae</em>&nbsp;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.</p>
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