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

Gomes, Tiago Araujo; da Silva, Tatiana Pereira; Machado, Edson; Vasconcelos, Sidra Ezidio Gonçalves; Mietto, Bruno Siqueira; de Faria Bertoluci, Daniela Ferreira; Rosa, Patricia Sammarco; Pinheiro, Roberta Olmo; Suffys, Philip Noel; Lery, Letícia Miranda Santos; Lara, Flavio Alves

doi:10.3390/pathogens13110986

Open AccessArticle

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

by

Tiago Araujo Gomes

^1,2,

Tatiana Pereira da Silva

^2,3,

Edson Machado

^2,4

,

Sidra Ezidio Gonçalves Vasconcelos

^2,4

,

Bruno Siqueira Mietto

⁵

,

Daniela Ferreira de Faria Bertoluci

⁶,

Patricia Sammarco Rosa

⁶,

Roberta Olmo Pinheiro

^2,3

,

Philip Noel Suffys

^2,4

,

Letícia Miranda Santos Lery

¹

and

Flavio Alves Lara

^1,2,*,†

¹

Laboratório de Microbiologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil

²

Rede de Micobactérias, Programa Inova-IOC, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil

³

Laboratório de Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil

⁴

Laboratório de Biologia Molecular Aplicada a Micobactérias, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro 21040-360, Brazil

⁵

Laboratório de Neurobiologia, Instituto de Ciências Biológicas, Universidade de Juiz de Fora, Juiz de Fora 36036-900, Brazil

⁶

Divisão de Pesquisa e Ensino, Instituto Lauro de Souza Lima, Bauru 17034-971, Brazil

^*

Author to whom correspondence should be addressed.

^†

Current address: Pavilhão Hanseníase, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Av. Brasil, 4365, sala 27, Rio de Janeiro 21040-360, Brazil.

Pathogens 2024, 13(11), 986; https://doi.org/10.3390/pathogens13110986

Submission received: 23 August 2024 / Revised: 16 September 2024 / Accepted: 18 September 2024 / Published: 12 November 2024

(This article belongs to the Special Issue Biology of Mycobacterial Pathogens)

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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.

Keywords: leprosy; non-synonymous mutations; single nucleotide polymorphs; SNPs; Thai-53; Br014-03; Br014-01

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MDPI and ACS Style

Gomes, T.A.; da Silva, T.P.; Machado, E.; Vasconcelos, S.E.G.; Mietto, B.S.; de Faria Bertoluci, D.F.; Rosa, P.S.; Pinheiro, R.O.; Suffys, P.N.; Lery, L.M.S.; et al. Genomic and Phenotypic Variations Among Thai-53 and Mycobacterium leprae Clinical Isolates: Implications for Leprosy Pathogenesis and Research. Pathogens 2024, 13, 986. https://doi.org/10.3390/pathogens13110986

AMA Style

Gomes TA, da Silva TP, Machado E, Vasconcelos SEG, Mietto BS, de Faria Bertoluci DF, Rosa PS, Pinheiro RO, Suffys PN, Lery LMS, et al. Genomic and Phenotypic Variations Among Thai-53 and Mycobacterium leprae Clinical Isolates: Implications for Leprosy Pathogenesis and Research. Pathogens. 2024; 13(11):986. https://doi.org/10.3390/pathogens13110986

Chicago/Turabian Style

Gomes, Tiago Araujo, 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, and et al. 2024. "Genomic and Phenotypic Variations Among Thai-53 and Mycobacterium leprae Clinical Isolates: Implications for Leprosy Pathogenesis and Research" Pathogens 13, no. 11: 986. https://doi.org/10.3390/pathogens13110986

APA Style

Gomes, T. A., da Silva, T. P., Machado, E., Vasconcelos, S. E. G., Mietto, B. S., de Faria Bertoluci, D. F., Rosa, P. S., Pinheiro, R. O., Suffys, P. N., Lery, L. M. S., & Lara, F. A. (2024). Genomic and Phenotypic Variations Among Thai-53 and Mycobacterium leprae Clinical Isolates: Implications for Leprosy Pathogenesis and Research. Pathogens, 13(11), 986. https://doi.org/10.3390/pathogens13110986

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

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