Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola
Abstract 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 A...
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| Format: | Article |
| Language: | English |
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BMC
2021-10-01
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| Series: | BMC Infectious Diseases |
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| Online Access: | https://doi.org/10.1186/s12879-021-06763-8 |
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| author | Ariadna Rando-Segura María Luisa Aznar María Milagros Moreno Mateu Espasa Soley Elena Sulleiro Igual Cristina Bocanegra Garcia Eva Gil Olivas Arlete Nindia Eugénio Carlos Escartin Huesca Adriano Zacarias Josep Vegue Collado Domingos Katimba Maria Carmen Vivas Cano Estevao Gabriel Maria Teresa López García Tomas Pumarola Suñe Israel Molina Romero María Teresa Tórtola Fernández |
| author_facet | Ariadna Rando-Segura María Luisa Aznar María Milagros Moreno Mateu Espasa Soley Elena Sulleiro Igual Cristina Bocanegra Garcia Eva Gil Olivas Arlete Nindia Eugénio Carlos Escartin Huesca Adriano Zacarias Josep Vegue Collado Domingos Katimba Maria Carmen Vivas Cano Estevao Gabriel Maria Teresa López García Tomas Pumarola Suñe Israel Molina Romero María Teresa Tórtola Fernández |
| author_sort | Ariadna Rando-Segura |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-12-22T13:47:42Z |
| format | Article |
| id | doaj.art-b6e259ce76e640bba2779583d7189f2a |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-12-22T13:47:42Z |
| publishDate | 2021-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-b6e259ce76e640bba2779583d7189f2a2022-12-21T18:23:45ZengBMCBMC Infectious Diseases1471-23342021-10-012111710.1186/s12879-021-06763-8Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of AngolaAriadna Rando-Segura0María Luisa Aznar1María Milagros Moreno2Mateu Espasa Soley3Elena Sulleiro Igual4Cristina Bocanegra Garcia5Eva Gil Olivas6Arlete Nindia Eugénio7Carlos Escartin Huesca8Adriano Zacarias9Josep Vegue Collado10Domingos Katimba11Maria Carmen Vivas Cano12Estevao Gabriel13Maria Teresa López García14Tomas Pumarola Suñe15Israel Molina Romero16María Teresa Tórtola Fernández17Microbiology Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaInfectious Disease Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaHospital Nossa Senhora da PazMicrobiology Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaMicrobiology Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaInfectious Disease Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaInfectious Disease Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaHospital Nossa Senhora da PazMicrobiology Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaHospital Nossa Senhora da PazMicrobiology Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaHospital Nossa Senhora da PazMicrobiology Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaHospital Nossa Senhora da PazHospital Nossa Senhora da PazMicrobiology Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaInfectious Disease Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaMicrobiology Department, Vall d’Hebron University Hospital, PROSICS Barcelona, Universitat Autònoma de BarcelonaAbstract 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.https://doi.org/10.1186/s12879-021-06763-8AngolaCubalGenoType MTBDRplus VER2.0ResistanceRifampicinrpoB mutations |
| spellingShingle | Ariadna Rando-Segura María Luisa Aznar María Milagros Moreno Mateu Espasa Soley Elena Sulleiro Igual Cristina Bocanegra Garcia Eva Gil Olivas Arlete Nindia Eugénio Carlos Escartin Huesca Adriano Zacarias Josep Vegue Collado Domingos Katimba Maria Carmen Vivas Cano Estevao Gabriel Maria Teresa López García Tomas Pumarola Suñe Israel Molina Romero María Teresa Tórtola Fernández Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola BMC Infectious Diseases Angola Cubal GenoType MTBDRplus VER2.0 Resistance Rifampicin rpoB mutations |
| 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 | Angola Cubal GenoType MTBDRplus VER2.0 Resistance Rifampicin rpoB mutations |
| url | https://doi.org/10.1186/s12879-021-06763-8 |
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