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Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola
BACKGROUND: The importance of Mycobacterium tuberculosis strains with disputed rpoB mutations remains to be defined. This study aimed to assess the frequency and types of rpoB mutations in M. tuberculosis isolates from Cubal, Angola, a country with a high incidence of tuberculosis. METHODS: All isol...
Autores principales: | , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507306/ https://www.ncbi.nlm.nih.gov/pubmed/34641802 http://dx.doi.org/10.1186/s12879-021-06763-8 |
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author | Rando-Segura, Ariadna Aznar, María Luisa Moreno, María Milagros Espasa Soley, Mateu Sulleiro Igual, Elena Bocanegra Garcia, Cristina Gil Olivas, Eva Nindia Eugénio, Arlete Escartin Huesca, Carlos Zacarias, Adriano Vegue Collado, Josep Katimba, Domingos Vivas Cano, Maria Carmen Gabriel, Estevao López García, Maria Teresa Pumarola Suñe, Tomas Molina Romero, Israel Tórtola Fernández, María Teresa |
author_facet | Rando-Segura, Ariadna Aznar, María Luisa Moreno, María Milagros Espasa Soley, Mateu Sulleiro Igual, Elena Bocanegra Garcia, Cristina Gil Olivas, Eva Nindia Eugénio, Arlete Escartin Huesca, Carlos Zacarias, Adriano Vegue Collado, Josep Katimba, Domingos Vivas Cano, Maria Carmen Gabriel, Estevao López García, Maria Teresa Pumarola Suñe, Tomas Molina Romero, Israel Tórtola Fernández, María Teresa |
author_sort | Rando-Segura, Ariadna |
collection | PubMed |
description | BACKGROUND: The importance of Mycobacterium tuberculosis strains with disputed rpoB mutations remains to be defined. This study aimed to assess the frequency and types of rpoB mutations in M. tuberculosis isolates from Cubal, Angola, a country with a high incidence of tuberculosis. METHODS: All isolates included (n = 308) were analyzed using phenotypic drug susceptibility testing and GenoType MTBDRplus assay. DNA sequencing of the rpoB gene and determination of rifampicin MIC by macrodilution method were additionally performed on isolates yielding discordant results (n = 12) and those in which the mutation detected was not characterized (n = 8). RESULTS: In total, 85.1% (74/87) of rifampicin-resistant strains had undisputed rpoB mutations -S450L (49), D435V (15), H445D (3), H445Y (2), Q432ins (1), L449M plus S450F (1), S450F (1), S450W (1) and S450Y (1)-; 10.3% (9/87) had disputed rpoB mutations—L430P plus S493L (1), N437del (1), H445L (3), D435Y (2), L452P (2)-, 2.3% (2.3%) showed no rpoB mutations and 2.3% (2/87) showed heteroresistance—D435Y plus L452P and L430P plus S493L-. CONCLUSION: Disputed rpoB mutations were common, occurring in 10.3% of rifampicin resistant isolates. Current phenotyping techniques may be unable to detect this resistance pattern. To increase their sensitivity, a lower concentration of RIF could be used in these tests or alternatively, rpoB mutations could be screened and characterized in all M. tuberculosis strains. |
format | Online Article Text |
id | pubmed-8507306 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-85073062021-10-20 Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola Rando-Segura, Ariadna Aznar, María Luisa Moreno, María Milagros Espasa Soley, Mateu Sulleiro Igual, Elena Bocanegra Garcia, Cristina Gil Olivas, Eva Nindia Eugénio, Arlete Escartin Huesca, Carlos Zacarias, Adriano Vegue Collado, Josep Katimba, Domingos Vivas Cano, Maria Carmen Gabriel, Estevao López García, Maria Teresa Pumarola Suñe, Tomas Molina Romero, Israel Tórtola Fernández, María Teresa BMC Infect Dis Research BACKGROUND: The importance of Mycobacterium tuberculosis strains with disputed rpoB mutations remains to be defined. This study aimed to assess the frequency and types of rpoB mutations in M. tuberculosis isolates from Cubal, Angola, a country with a high incidence of tuberculosis. METHODS: All isolates included (n = 308) were analyzed using phenotypic drug susceptibility testing and GenoType MTBDRplus assay. DNA sequencing of the rpoB gene and determination of rifampicin MIC by macrodilution method were additionally performed on isolates yielding discordant results (n = 12) and those in which the mutation detected was not characterized (n = 8). RESULTS: In total, 85.1% (74/87) of rifampicin-resistant strains had undisputed rpoB mutations -S450L (49), D435V (15), H445D (3), H445Y (2), Q432ins (1), L449M plus S450F (1), S450F (1), S450W (1) and S450Y (1)-; 10.3% (9/87) had disputed rpoB mutations—L430P plus S493L (1), N437del (1), H445L (3), D435Y (2), L452P (2)-, 2.3% (2.3%) showed no rpoB mutations and 2.3% (2/87) showed heteroresistance—D435Y plus L452P and L430P plus S493L-. CONCLUSION: Disputed rpoB mutations were common, occurring in 10.3% of rifampicin resistant isolates. Current phenotyping techniques may be unable to detect this resistance pattern. To increase their sensitivity, a lower concentration of RIF could be used in these tests or alternatively, rpoB mutations could be screened and characterized in all M. tuberculosis strains. BioMed Central 2021-10-12 /pmc/articles/PMC8507306/ /pubmed/34641802 http://dx.doi.org/10.1186/s12879-021-06763-8 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Rando-Segura, Ariadna Aznar, María Luisa Moreno, María Milagros Espasa Soley, Mateu Sulleiro Igual, Elena Bocanegra Garcia, Cristina Gil Olivas, Eva Nindia Eugénio, Arlete Escartin Huesca, Carlos Zacarias, Adriano Vegue Collado, Josep Katimba, Domingos Vivas Cano, Maria Carmen Gabriel, Estevao López García, Maria Teresa Pumarola Suñe, Tomas Molina Romero, Israel Tórtola Fernández, María Teresa Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola |
title | Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola |
title_full | Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola |
title_fullStr | Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola |
title_full_unstemmed | Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola |
title_short | Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola |
title_sort | molecular characterization of rpob gene mutations in isolates from tuberculosis patients in cubal, republic of angola |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507306/ https://www.ncbi.nlm.nih.gov/pubmed/34641802 http://dx.doi.org/10.1186/s12879-021-06763-8 |
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