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...

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Detalles Bibliográficos
Autores: Rando-Segura, Ariadna|||0000-0003-4555-7286, Aznar, Maria Luisa|||0000-0001-9223-7790, Moreno, María Milagros, Espasa, Mateu|||0000-0003-4822-1024, Sulleiro, Elena|||0000-0002-9783-6060, Bocanegra García, Cristina, Gil Olivas, Eva|||0000-0001-5788-5602, Nindia Eugénio, Arlete, Escartin Huesca, Carlos, Zacarias, Adriano, Vegue Collado, Josep, Katimba, Domingos, Vivas Cano, Maria Carmen, Gabriel, Estevao, López García, Teresa, Pumarola Suñé, Tomàs|||0000-0002-5171-7461, Molina Romero, Israel|||0000-0001-6642-7515, Tórtola Fernández, María Teresa|||0000-0002-9188-298X
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:293201
Acceso en línea:https://ddd.uab.cat/record/293201
https://dx.doi.org/urn:doi:10.1186/s12879-021-06763-8
Access Level:acceso abierto
Palabra clave:Angola
Cubal
GenoType MTBDRplus VER2.0
Resistance
Rifampicin
RpoB mutations
Descripción
Sumario: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.

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