Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs

Autores
Imperiale, Belén Rocío; Zumárraga, Martín José; Di Giulio, A. B.; Cataldi, Ángel Adrián; Morcillo, Nora Susana
Año de publicación
2013
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
SETTING: Dr Cetrángolo Hospital, Buenos Aires, Argentina. OBJECTIVES: To characterise drug-resistant (DR), multidrug-resistant (MDR-) and extensively drug-resistant (XDR-) Mycobacterium tuberculosis isolates, and identify their genetic profiles, drug resistance levels and resistance- conferring mutations. DESIGN: Phenotypic drug susceptibility testing methods were used to determine drug resistance profiles. Minimal inhibitory concentrations (MICs) of isoniazid (INH), rifampicin (RMP) and levofloxacin (LVX) from 169 DR tuberculosis (TB) isolates, 78 of them monoresistant to INH, 13 to RMP, 7 to LVX, and 71 MDR-TB, were determined. Multiplex allele-specific polymerase chain reaction and DNA sequencing were used to detect mutations in katG, rpoB and gyrA/B genes. Genotyping was performed using spoligotyping and insertion sequence 6110 restriction fragment length polymorphism. RESULTS: In total, 38.9% of the INH-resistant (INHR) isolates had an MIC ≥ 32 μg/ml; 61.3% of the RMP-resistant (RMPR) isolates had an MIC ≥ 64 μg/ml and 55.6% of the LVX-r esistant (LVXR) isolates had an MIC 4-≥16 μg/ml. The main mutations found in INHR isolates were katG315 (53.7%) and inhAP-15 (25.5%), whereas in RMPR isolates the main mutations were rpoB531 (61.9%), followed by rpoB526 (16.7%). LVX R isolates showed mutations in gyrA94/90. Haarlem, LAM and T were the main spoligotyping families found. katG315 was mainly associated with Haarlem and LAM, whereas inhAP-15 was associated with T. CONCLUSIONS: Several isolates showed an association between high INHR levels and katG mutation; others from the Haarlem family were prone to becoming MDR-TB and continue to circulate in the community.
Fil: Imperiale, Belén Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; Argentina
Fil: Zumárraga, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria; Argentina
Fil: Di Giulio, A. B.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General Agudos "Petrona V. De Cordero"; Argentina
Fil: Cataldi, Ángel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria; Argentina
Fil: Morcillo, Nora. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; Argentina
Materia
Drug Resistance Levels
Genetic Mutations
Genotypes
M. Tuberculosis
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/25273
Acceder
id CONICETDig_9a219fef9f5afb0bbcc670c7d879bc24
oai_identifier_str oai:ri.conicet.gov.ar:11336/25273
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugsImperiale, Belén RocíoZumárraga, Martín JoséDi Giulio, A. B.Cataldi, Ángel AdriánMorcillo, Nora SusanaDrug Resistance LevelsGenetic MutationsGenotypesM. Tuberculosishttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3SETTING: Dr Cetrángolo Hospital, Buenos Aires, Argentina. OBJECTIVES: To characterise drug-resistant (DR), multidrug-resistant (MDR-) and extensively drug-resistant (XDR-) Mycobacterium tuberculosis isolates, and identify their genetic profiles, drug resistance levels and resistance- conferring mutations. DESIGN: Phenotypic drug susceptibility testing methods were used to determine drug resistance profiles. Minimal inhibitory concentrations (MICs) of isoniazid (INH), rifampicin (RMP) and levofloxacin (LVX) from 169 DR tuberculosis (TB) isolates, 78 of them monoresistant to INH, 13 to RMP, 7 to LVX, and 71 MDR-TB, were determined. Multiplex allele-specific polymerase chain reaction and DNA sequencing were used to detect mutations in katG, rpoB and gyrA/B genes. Genotyping was performed using spoligotyping and insertion sequence 6110 restriction fragment length polymorphism. RESULTS: In total, 38.9% of the INH-resistant (INHR) isolates had an MIC ≥ 32 μg/ml; 61.3% of the RMP-resistant (RMPR) isolates had an MIC ≥ 64 μg/ml and 55.6% of the LVX-r esistant (LVXR) isolates had an MIC 4-≥16 μg/ml. The main mutations found in INHR isolates were katG315 (53.7%) and inhAP-15 (25.5%), whereas in RMPR isolates the main mutations were rpoB531 (61.9%), followed by rpoB526 (16.7%). LVX R isolates showed mutations in gyrA94/90. Haarlem, LAM and T were the main spoligotyping families found. katG315 was mainly associated with Haarlem and LAM, whereas inhAP-15 was associated with T. CONCLUSIONS: Several isolates showed an association between high INHR levels and katG mutation; others from the Haarlem family were prone to becoming MDR-TB and continue to circulate in the community.Fil: Imperiale, Belén Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; ArgentinaFil: Zumárraga, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Di Giulio, A. B.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General Agudos "Petrona V. De Cordero"; ArgentinaFil: Cataldi, Ángel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria; ArgentinaFil: Morcillo, Nora. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; ArgentinaInternational Union Against Tuberculosis and Lung Disease2013-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/25273Imperiale, Belén Rocío; Zumárraga, Martín José; Di Giulio, A. B.; Cataldi, Ángel Adrián; Morcillo, Nora Susana; Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs; International Union Against Tuberculosis and Lung Disease; International Journal of Tuberculosis and Lung Disease; 17; 8; 8-2013; 1088-10931027-3719CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://www.ingentaconnect.com/content/iuatld/ijtld/2013/00000017/00000008/art00017info:eu-repo/semantics/altIdentifier/doi/10.5588/ijtld.12.0949info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T10:04:58Zoai:ri.conicet.gov.ar:11336/25273instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 10:04:58.821CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs
title Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs
spellingShingle Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs
Imperiale, Belén Rocío
Drug Resistance Levels
Genetic Mutations
Genotypes
M. Tuberculosis
title_short Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs
title_full Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs
title_fullStr Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs
title_full_unstemmed Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs
title_sort Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs
dc.creator.none.fl_str_mv Imperiale, Belén Rocío
Zumárraga, Martín José
Di Giulio, A. B.
Cataldi, Ángel Adrián
Morcillo, Nora Susana
author Imperiale, Belén Rocío
author_facet Imperiale, Belén Rocío
Zumárraga, Martín José
Di Giulio, A. B.
Cataldi, Ángel Adrián
Morcillo, Nora Susana
author_role author
author2 Zumárraga, Martín José
Di Giulio, A. B.
Cataldi, Ángel Adrián
Morcillo, Nora Susana
author2_role author
author
author
author
dc.subject.none.fl_str_mv Drug Resistance Levels
Genetic Mutations
Genotypes
M. Tuberculosis
topic Drug Resistance Levels
Genetic Mutations
Genotypes
M. Tuberculosis
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv SETTING: Dr Cetrángolo Hospital, Buenos Aires, Argentina. OBJECTIVES: To characterise drug-resistant (DR), multidrug-resistant (MDR-) and extensively drug-resistant (XDR-) Mycobacterium tuberculosis isolates, and identify their genetic profiles, drug resistance levels and resistance- conferring mutations. DESIGN: Phenotypic drug susceptibility testing methods were used to determine drug resistance profiles. Minimal inhibitory concentrations (MICs) of isoniazid (INH), rifampicin (RMP) and levofloxacin (LVX) from 169 DR tuberculosis (TB) isolates, 78 of them monoresistant to INH, 13 to RMP, 7 to LVX, and 71 MDR-TB, were determined. Multiplex allele-specific polymerase chain reaction and DNA sequencing were used to detect mutations in katG, rpoB and gyrA/B genes. Genotyping was performed using spoligotyping and insertion sequence 6110 restriction fragment length polymorphism. RESULTS: In total, 38.9% of the INH-resistant (INHR) isolates had an MIC ≥ 32 μg/ml; 61.3% of the RMP-resistant (RMPR) isolates had an MIC ≥ 64 μg/ml and 55.6% of the LVX-r esistant (LVXR) isolates had an MIC 4-≥16 μg/ml. The main mutations found in INHR isolates were katG315 (53.7%) and inhAP-15 (25.5%), whereas in RMPR isolates the main mutations were rpoB531 (61.9%), followed by rpoB526 (16.7%). LVX R isolates showed mutations in gyrA94/90. Haarlem, LAM and T were the main spoligotyping families found. katG315 was mainly associated with Haarlem and LAM, whereas inhAP-15 was associated with T. CONCLUSIONS: Several isolates showed an association between high INHR levels and katG mutation; others from the Haarlem family were prone to becoming MDR-TB and continue to circulate in the community.
Fil: Imperiale, Belén Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; Argentina
Fil: Zumárraga, Martín José. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria; Argentina
Fil: Di Giulio, A. B.. Provincia de Buenos Aires. Ministerio de Salud. Hospital Zonal General Agudos "Petrona V. De Cordero"; Argentina
Fil: Cataldi, Ángel Adrián. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto Nacional de Tecnología Agropecuaria; Argentina
Fil: Morcillo, Nora. Provincia de Buenos Aires. Ministerio de Salud. Hospital "Dr. Antonio A. Cetrángolo"; Argentina
description SETTING: Dr Cetrángolo Hospital, Buenos Aires, Argentina. OBJECTIVES: To characterise drug-resistant (DR), multidrug-resistant (MDR-) and extensively drug-resistant (XDR-) Mycobacterium tuberculosis isolates, and identify their genetic profiles, drug resistance levels and resistance- conferring mutations. DESIGN: Phenotypic drug susceptibility testing methods were used to determine drug resistance profiles. Minimal inhibitory concentrations (MICs) of isoniazid (INH), rifampicin (RMP) and levofloxacin (LVX) from 169 DR tuberculosis (TB) isolates, 78 of them monoresistant to INH, 13 to RMP, 7 to LVX, and 71 MDR-TB, were determined. Multiplex allele-specific polymerase chain reaction and DNA sequencing were used to detect mutations in katG, rpoB and gyrA/B genes. Genotyping was performed using spoligotyping and insertion sequence 6110 restriction fragment length polymorphism. RESULTS: In total, 38.9% of the INH-resistant (INHR) isolates had an MIC ≥ 32 μg/ml; 61.3% of the RMP-resistant (RMPR) isolates had an MIC ≥ 64 μg/ml and 55.6% of the LVX-r esistant (LVXR) isolates had an MIC 4-≥16 μg/ml. The main mutations found in INHR isolates were katG315 (53.7%) and inhAP-15 (25.5%), whereas in RMPR isolates the main mutations were rpoB531 (61.9%), followed by rpoB526 (16.7%). LVX R isolates showed mutations in gyrA94/90. Haarlem, LAM and T were the main spoligotyping families found. katG315 was mainly associated with Haarlem and LAM, whereas inhAP-15 was associated with T. CONCLUSIONS: Several isolates showed an association between high INHR levels and katG mutation; others from the Haarlem family were prone to becoming MDR-TB and continue to circulate in the community.
publishDate 2013
dc.date.none.fl_str_mv 2013-08
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/25273
Imperiale, Belén Rocío; Zumárraga, Martín José; Di Giulio, A. B.; Cataldi, Ángel Adrián; Morcillo, Nora Susana; Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs; International Union Against Tuberculosis and Lung Disease; International Journal of Tuberculosis and Lung Disease; 17; 8; 8-2013; 1088-1093
1027-3719
CONICET Digital
CONICET
url http://hdl.handle.net/11336/25273
identifier_str_mv Imperiale, Belén Rocío; Zumárraga, Martín José; Di Giulio, A. B.; Cataldi, Ángel Adrián; Morcillo, Nora Susana; Molecular and phenotypic characterisation of Mycobacterium tuberculosis resistant to anti-tuberculosis drugs; International Union Against Tuberculosis and Lung Disease; International Journal of Tuberculosis and Lung Disease; 17; 8; 8-2013; 1088-1093
1027-3719
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://www.ingentaconnect.com/content/iuatld/ijtld/2013/00000017/00000008/art00017
info:eu-repo/semantics/altIdentifier/doi/10.5588/ijtld.12.0949
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv International Union Against Tuberculosis and Lung Disease
publisher.none.fl_str_mv International Union Against Tuberculosis and Lung Disease
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269884145205248
score 13.13397

Publicaciones similares