A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs I...
- Autores
- Franceschelli, Jorgelina Judith; Belardinelli, Juan Manuel; Tong, Ping; Loftus, Brendan; Recio Balsells, Alejandro Iván; Labadie, Guillermo Roberto; Gordon, Stephen V.; Morbidoni, Héctor Ricardo
- Año de publicación
- 2018
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Clinical isolates of Mycobacterium tuberculosis and Mycobacterium bovis are differentially susceptible to 2-Thiophen Hydrazide (TCH); however its mechanism of action or the reasons for that difference are unknown. We report herein that under our experimental conditions, TCH inhibits M. tuberculosis in solid but not in liquid medium, and that in spite of resembling Isoniazid and Ethionamide, it does not affect mycolic acid synthesis. To understand the mechanisms of action of TCH we isolated M. tuberculosis TCH resistant mutants which fell into two groups; one resistant to TCH and Isoniazid but not to Ethionamide or Triclosan, and the other resistant only to TCH with no, or marginal, cross resistance to Isoniazid. A S315T katG mutation conferred resistance to TCH while katG expression from a plasmid reduced M. tuberculosis MIC to this drug, suggesting a possible involvement of KatG in TCH activation. Whole genome sequencing of mutants from this second group revealed a single mutation in the alkylhydroperoxide reductase ahpC promoter locus in half of the mutants, while the remaining contained mutations in dispensable genes. This is the first report of the genetics underlying the action of TCH and of the involvement of ahpC as the sole basis for resistance to an anti-tubercular compound.
Fil: Franceschelli, Jorgelina Judith. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina
Fil: Belardinelli, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. State University of Colorado - Fort Collins; Estados Unidos
Fil: Tong, Ping. University College Dublin; Irlanda. University of Edinburgh; Reino Unido
Fil: Loftus, Brendan. University College Dublin; Irlanda
Fil: Recio Balsells, Alejandro Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Labadie, Guillermo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina
Fil: Gordon, Stephen V.. University College Dublin; Irlanda
Fil: Morbidoni, Héctor Ricardo. Universidad Nacional de Rosario; Argentina - Materia
-
2-THIOPHEN CARBOXYLIC ACID HYDRAZIDE
ALKYLHYDROPEROXIDASE
MYCOBACTERIUM BOVIS
MYCOBACTERIUM TUBERCULOSIS
NON TUBERCULOUS MYCOBACTERIA
TCH RESISTANT MUTANTS - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/91966
Ver los metadatos del registro completo
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oai:ri.conicet.gov.ar:11336/91966 |
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network_name_str |
CONICET Digital (CONICET) |
spelling |
A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and EthionamideFranceschelli, Jorgelina JudithBelardinelli, Juan ManuelTong, PingLoftus, BrendanRecio Balsells, Alejandro IvánLabadie, Guillermo RobertoGordon, Stephen V.Morbidoni, Héctor Ricardo2-THIOPHEN CARBOXYLIC ACID HYDRAZIDEALKYLHYDROPEROXIDASEMYCOBACTERIUM BOVISMYCOBACTERIUM TUBERCULOSISNON TUBERCULOUS MYCOBACTERIATCH RESISTANT MUTANTShttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Clinical isolates of Mycobacterium tuberculosis and Mycobacterium bovis are differentially susceptible to 2-Thiophen Hydrazide (TCH); however its mechanism of action or the reasons for that difference are unknown. We report herein that under our experimental conditions, TCH inhibits M. tuberculosis in solid but not in liquid medium, and that in spite of resembling Isoniazid and Ethionamide, it does not affect mycolic acid synthesis. To understand the mechanisms of action of TCH we isolated M. tuberculosis TCH resistant mutants which fell into two groups; one resistant to TCH and Isoniazid but not to Ethionamide or Triclosan, and the other resistant only to TCH with no, or marginal, cross resistance to Isoniazid. A S315T katG mutation conferred resistance to TCH while katG expression from a plasmid reduced M. tuberculosis MIC to this drug, suggesting a possible involvement of KatG in TCH activation. Whole genome sequencing of mutants from this second group revealed a single mutation in the alkylhydroperoxide reductase ahpC promoter locus in half of the mutants, while the remaining contained mutations in dispensable genes. This is the first report of the genetics underlying the action of TCH and of the involvement of ahpC as the sole basis for resistance to an anti-tubercular compound.Fil: Franceschelli, Jorgelina Judith. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; ArgentinaFil: Belardinelli, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. State University of Colorado - Fort Collins; Estados UnidosFil: Tong, Ping. University College Dublin; Irlanda. University of Edinburgh; Reino UnidoFil: Loftus, Brendan. University College Dublin; IrlandaFil: Recio Balsells, Alejandro Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Labadie, Guillermo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Gordon, Stephen V.. University College Dublin; IrlandaFil: Morbidoni, Héctor Ricardo. Universidad Nacional de Rosario; ArgentinaChurchill Livingstone2018-09info: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/11336/91966Franceschelli, Jorgelina Judith; Belardinelli, Juan Manuel; Tong, Ping; Loftus, Brendan; Recio Balsells, Alejandro Iván; et al.; A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide; Churchill Livingstone; Tuberculosis (Edinb); 112; 9-2018; 69-781472-9792CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.tube.2018.08.001info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1472979218301598info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:51:33Zoai:ri.conicet.gov.ar:11336/91966instacron: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:34982025-09-29 09:51:33.349CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide |
title |
A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide |
spellingShingle |
A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide Franceschelli, Jorgelina Judith 2-THIOPHEN CARBOXYLIC ACID HYDRAZIDE ALKYLHYDROPEROXIDASE MYCOBACTERIUM BOVIS MYCOBACTERIUM TUBERCULOSIS NON TUBERCULOUS MYCOBACTERIA TCH RESISTANT MUTANTS |
title_short |
A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide |
title_full |
A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide |
title_fullStr |
A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide |
title_full_unstemmed |
A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide |
title_sort |
A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide |
dc.creator.none.fl_str_mv |
Franceschelli, Jorgelina Judith Belardinelli, Juan Manuel Tong, Ping Loftus, Brendan Recio Balsells, Alejandro Iván Labadie, Guillermo Roberto Gordon, Stephen V. Morbidoni, Héctor Ricardo |
author |
Franceschelli, Jorgelina Judith |
author_facet |
Franceschelli, Jorgelina Judith Belardinelli, Juan Manuel Tong, Ping Loftus, Brendan Recio Balsells, Alejandro Iván Labadie, Guillermo Roberto Gordon, Stephen V. Morbidoni, Héctor Ricardo |
author_role |
author |
author2 |
Belardinelli, Juan Manuel Tong, Ping Loftus, Brendan Recio Balsells, Alejandro Iván Labadie, Guillermo Roberto Gordon, Stephen V. Morbidoni, Héctor Ricardo |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
2-THIOPHEN CARBOXYLIC ACID HYDRAZIDE ALKYLHYDROPEROXIDASE MYCOBACTERIUM BOVIS MYCOBACTERIUM TUBERCULOSIS NON TUBERCULOUS MYCOBACTERIA TCH RESISTANT MUTANTS |
topic |
2-THIOPHEN CARBOXYLIC ACID HYDRAZIDE ALKYLHYDROPEROXIDASE MYCOBACTERIUM BOVIS MYCOBACTERIUM TUBERCULOSIS NON TUBERCULOUS MYCOBACTERIA TCH RESISTANT MUTANTS |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Clinical isolates of Mycobacterium tuberculosis and Mycobacterium bovis are differentially susceptible to 2-Thiophen Hydrazide (TCH); however its mechanism of action or the reasons for that difference are unknown. We report herein that under our experimental conditions, TCH inhibits M. tuberculosis in solid but not in liquid medium, and that in spite of resembling Isoniazid and Ethionamide, it does not affect mycolic acid synthesis. To understand the mechanisms of action of TCH we isolated M. tuberculosis TCH resistant mutants which fell into two groups; one resistant to TCH and Isoniazid but not to Ethionamide or Triclosan, and the other resistant only to TCH with no, or marginal, cross resistance to Isoniazid. A S315T katG mutation conferred resistance to TCH while katG expression from a plasmid reduced M. tuberculosis MIC to this drug, suggesting a possible involvement of KatG in TCH activation. Whole genome sequencing of mutants from this second group revealed a single mutation in the alkylhydroperoxide reductase ahpC promoter locus in half of the mutants, while the remaining contained mutations in dispensable genes. This is the first report of the genetics underlying the action of TCH and of the involvement of ahpC as the sole basis for resistance to an anti-tubercular compound. Fil: Franceschelli, Jorgelina Judith. Universidad Nacional de Rosario; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina Fil: Belardinelli, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario; Argentina. State University of Colorado - Fort Collins; Estados Unidos Fil: Tong, Ping. University College Dublin; Irlanda. University of Edinburgh; Reino Unido Fil: Loftus, Brendan. University College Dublin; Irlanda Fil: Recio Balsells, Alejandro Iván. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Labadie, Guillermo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina Fil: Gordon, Stephen V.. University College Dublin; Irlanda Fil: Morbidoni, Héctor Ricardo. Universidad Nacional de Rosario; Argentina |
description |
Clinical isolates of Mycobacterium tuberculosis and Mycobacterium bovis are differentially susceptible to 2-Thiophen Hydrazide (TCH); however its mechanism of action or the reasons for that difference are unknown. We report herein that under our experimental conditions, TCH inhibits M. tuberculosis in solid but not in liquid medium, and that in spite of resembling Isoniazid and Ethionamide, it does not affect mycolic acid synthesis. To understand the mechanisms of action of TCH we isolated M. tuberculosis TCH resistant mutants which fell into two groups; one resistant to TCH and Isoniazid but not to Ethionamide or Triclosan, and the other resistant only to TCH with no, or marginal, cross resistance to Isoniazid. A S315T katG mutation conferred resistance to TCH while katG expression from a plasmid reduced M. tuberculosis MIC to this drug, suggesting a possible involvement of KatG in TCH activation. Whole genome sequencing of mutants from this second group revealed a single mutation in the alkylhydroperoxide reductase ahpC promoter locus in half of the mutants, while the remaining contained mutations in dispensable genes. This is the first report of the genetics underlying the action of TCH and of the involvement of ahpC as the sole basis for resistance to an anti-tubercular compound. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-09 |
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/11336/91966 Franceschelli, Jorgelina Judith; Belardinelli, Juan Manuel; Tong, Ping; Loftus, Brendan; Recio Balsells, Alejandro Iván; et al.; A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide; Churchill Livingstone; Tuberculosis (Edinb); 112; 9-2018; 69-78 1472-9792 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/91966 |
identifier_str_mv |
Franceschelli, Jorgelina Judith; Belardinelli, Juan Manuel; Tong, Ping; Loftus, Brendan; Recio Balsells, Alejandro Iván; et al.; A katG S315T or an ahpC promoter mutation mediate Mycobacterium tuberculosis resistance to 2-thiophen carboxylic acid hydrazide, an inhibitor resembling the anti-tubercular drugs Isoniazid and Ethionamide; Churchill Livingstone; Tuberculosis (Edinb); 112; 9-2018; 69-78 1472-9792 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.tube.2018.08.001 info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S1472979218301598 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Churchill Livingstone |
publisher.none.fl_str_mv |
Churchill Livingstone |
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 |
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1844613584889315328 |
score |
13.070432 |