Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing
| Main Author: | |
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| Publication Date: | 2024 |
| Other Authors: | , , , , , , , , , , , , , , , , |
| Format: | Article |
| Language: | eng |
| Source: | Repositório Institucional da FIOCRUZ (ARCA) |
| DOI: | 10.3390/antibiotics13060496 |
| Download full: | https://arca.fiocruz.br/handle/icict/64799 |
Summary: | Produção científica do Laboratório de Biologia Molecular Aplicada a Micobactérias. |
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Esteves, Leonardo SouzaGomes, Lia LimaBrites, DanielaFandinho, Fátima Cristina OnofreSilva, Marcela Lopes Bhering daPereira, Márcia Aparecida da SilvaConceição, Emilyn CostaSalvato, Richard SteinerCosta, Bianca Porphírio daMedeiros, Reginalda Ferreira de MeloCaldas, Paulo Cesar de SouzaRedner, PauloDalcolmo, Margareth Maria PrettiEldholm, VegardGagneux, SebastienRossetti, Maria Lucia RosaKritski, Afrânio LineuSuffys, Philip Noel2024-07-02T18:21:44Z2024-07-02T18:21:44Z2024ESTEVES, Leonardo Souza et al. Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing. Antibiotics, v. 13, n. 6, p. 1-22, 28 May 2024.2079-6382https://arca.fiocruz.br/handle/icict/6479910.3390/antibiotics130604962079-6382Produção científica do Laboratório de Biologia Molecular Aplicada a Micobactérias.This research was funded by Coordination for the Improvement of Higher Education Personnel (CAPES/MEC/Brazil) and to the National Council for Scientific and Technological Development (CNPq/MCTI/Brazil). Leonardo Souza Esteves was supported by doctorate and sandwich doctorate scholarship 888881.134437/2016-01 (CAPES/Brazil-UFRJ/PPG Clínica Médica, Coordinator: José R. Lapa e Silva), and postdoctoral fellowship by Programa Fiocruz de Fomento à Inovação (INOVA/Fiocruz).Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil / Governo do Estado Rio Grande do Sul. Secretaria Estadual da Saúde. Centro Estadual de Vigilância em Saúde. Centro de Desenvolvimento Científico e Tecnológico. Porto Alegre, RS, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.Swiss Tropical and Public Health Institute. Allschwil, Switzerland / University of Basel. Basel, Switzerland.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Rio de Janeiro, RJ, Brasil.Stellenbosch University. Faculty of Medicine and Health Sciences. Division of Molecular Biology and Human Genetics. Centre for Tuberculosis Research. South African Medical Research Council. National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research. Department of Science and Innovation. Cape Town, South Africa.Governo do Estado Rio Grande do Sul. Secretaria Estadual da Saúde. Centro Estadual de Vigilância em Saúde. Centro de Desenvolvimento Científico e Tecnológico. Porto Alegre, RS, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Escola Nacional de Saúde Pública Sergio Arouca. Centro de Referência Professor Hélio Fraga. Rio de Janeiro, RJ, Brasil.Norwegian Institute of Public Health. Oslo, Norway.Swiss Tropical and Public Health Institute. Allschwil, Switzerland / University of Basel. Basel, Switzerland.Universidade Luterana do Brasil. Laboratório de Biologia Molecular. Canoas, RS, Brasil.Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Faculdade de Medicina. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular Aplicada a Micobactérias. Rio de Janeiro, RJ, Brasil.The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug-resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensive resistance (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides the analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definitions. Sub-lineage 4.3 (52%) was the most frequent genotype, and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected twenty novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. A cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug resistance prediction, presenting the best accuracy values for five of the nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) or genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil and the genetic and clinical data correlations and demonstrated its utility for surveillance efforts regarding the spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.engMDPIGenetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencinginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleMycobacterium tuberculosisDrug resistanceWhole-genome sequencingGenetic diversityBrazilNovel mutations10 Redução das desigualdadesinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://arca.fiocruz.br/bitstreams/6858e603-3b24-4c0e-9a9f-1972c7f2791d/download5a560609d32a3863062d77ff32785d58MD51falseAnonymousREADORIGINALve_Leonardo_Esteves_etal_IOC_2024.pdfve_Leonardo_Esteves_etal_IOC_2024.pdfapplication/pdf1387229https://arca.fiocruz.br/bitstreams/6ec5c979-5036-453b-ad0a-a8f20100fc96/downloadd246896f4ef1d2aad6cde80b338b479aMD52trueAnonymousREADTHUMBNAILcapa_Leonardo_Esteves_etal_IOC_2024.jpgcapa_Leonardo_Esteves_etal_IOC_2024.jpgCapaimage/jpeg1075275https://arca.fiocruz.br/bitstreams/97c81aa6-74ac-42dd-aa40-3d3c9e5ba193/download34727e8bb5b8126bf907402b300b3317MD53falseAnonymousREADve_Leonardo_Esteves_etal_IOC_2024.pdf.jpgve_Leonardo_Esteves_etal_IOC_2024.pdf.jpgGenerated Thumbnailimage/jpeg4908https://arca.fiocruz.br/bitstreams/1e95c563-aeea-4290-8840-a9b7f1e22231/download7126a4d12cff7ee3ffe69dc70064ac95MD511falseAnonymousREADTEXTve_Leonardo_Esteves_etal_IOC_2024.pdf.txtve_Leonardo_Esteves_etal_IOC_2024.pdf.txtExtracted texttext/plain100371https://arca.fiocruz.br/bitstreams/885b3985-c7ac-4394-bf3b-c2893ba19f1d/download650483b408c6481b227d88b9a7920525MD510falseAnonymousREADicict/647992025-07-29 23:22:05.662open.accessoai:arca.fiocruz.br:icict/64799https://arca.fiocruz.brRepositório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352025-07-30T02:22:05Repositório Institucional da FIOCRUZ (ARCA) - 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| dc.title.none.fl_str_mv |
Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing |
| title |
Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing |
| spellingShingle |
Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing Esteves, Leonardo Souza Mycobacterium tuberculosis Drug resistance Whole-genome sequencing Genetic diversity Brazil Novel mutations 10 Redução das desigualdades |
| title_short |
Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing |
| title_full |
Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing |
| title_fullStr |
Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing |
| title_full_unstemmed |
Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing |
| title_sort |
Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing |
| author |
Esteves, Leonardo Souza |
| author_facet |
Esteves, Leonardo Souza Gomes, Lia Lima Brites, Daniela Fandinho, Fátima Cristina Onofre Silva, Marcela Lopes Bhering da Pereira, Márcia Aparecida da Silva Conceição, Emilyn Costa Salvato, Richard Steiner Costa, Bianca Porphírio da Medeiros, Reginalda Ferreira de Melo Caldas, Paulo Cesar de Souza Redner, Paulo Dalcolmo, Margareth Maria Pretti Eldholm, Vegard Gagneux, Sebastien Rossetti, Maria Lucia Rosa Kritski, Afrânio Lineu Suffys, Philip Noel |
| author_role |
author |
| author2 |
Gomes, Lia Lima Brites, Daniela Fandinho, Fátima Cristina Onofre Silva, Marcela Lopes Bhering da Pereira, Márcia Aparecida da Silva Conceição, Emilyn Costa Salvato, Richard Steiner Costa, Bianca Porphírio da Medeiros, Reginalda Ferreira de Melo Caldas, Paulo Cesar de Souza Redner, Paulo Dalcolmo, Margareth Maria Pretti Eldholm, Vegard Gagneux, Sebastien Rossetti, Maria Lucia Rosa Kritski, Afrânio Lineu Suffys, Philip Noel |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Esteves, Leonardo Souza Gomes, Lia Lima Brites, Daniela Fandinho, Fátima Cristina Onofre Silva, Marcela Lopes Bhering da Pereira, Márcia Aparecida da Silva Conceição, Emilyn Costa Salvato, Richard Steiner Costa, Bianca Porphírio da Medeiros, Reginalda Ferreira de Melo Caldas, Paulo Cesar de Souza Redner, Paulo Dalcolmo, Margareth Maria Pretti Eldholm, Vegard Gagneux, Sebastien Rossetti, Maria Lucia Rosa Kritski, Afrânio Lineu Suffys, Philip Noel |
| dc.subject.en.none.fl_str_mv |
Mycobacterium tuberculosis Drug resistance Whole-genome sequencing Genetic diversity Brazil Novel mutations |
| topic |
Mycobacterium tuberculosis Drug resistance Whole-genome sequencing Genetic diversity Brazil Novel mutations 10 Redução das desigualdades |
| dc.subject.ods.none.fl_str_mv |
10 Redução das desigualdades |
| description |
Produção científica do Laboratório de Biologia Molecular Aplicada a Micobactérias. |
| publishDate |
2024 |
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2024-07-02T18:21:44Z |
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2024-07-02T18:21:44Z |
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2024 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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ESTEVES, Leonardo Souza et al. Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing. Antibiotics, v. 13, n. 6, p. 1-22, 28 May 2024. |
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https://arca.fiocruz.br/handle/icict/64799 |
| dc.identifier.issn.none.fl_str_mv |
2079-6382 |
| dc.identifier.doi.none.fl_str_mv |
10.3390/antibiotics13060496 |
| dc.identifier.eissn.none.fl_str_mv |
2079-6382 |
| identifier_str_mv |
ESTEVES, Leonardo Souza et al. Genetic characterization and population structure of drug-resistant Mycobacterium tuberculosis isolated from brazilian patients using whole-genome sequencing. Antibiotics, v. 13, n. 6, p. 1-22, 28 May 2024. 2079-6382 10.3390/antibiotics13060496 |
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MDPI |
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MDPI |
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