Reversion of antibiotic resistance in Mycobacterium tuberculosis by spiroisoxazoline SMARt-420-Reference-Cited by-同舟云学术

Reversion of antibiotic resistance in Mycobacterium tuberculosis by spiroisoxazoline SMARt-420

Published:2017-03-17 Issue:6330 Volume:355 Page:1206-1211
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Blondiaux Nicolas¹^ORCID,Moune Martin¹^ORCID,Desroses Matthieu²³^ORCID,Frita Rosangela¹^ORCID,Flipo Marion²^ORCID,Mathys Vanessa⁴,Soetaert Karine⁴,Kiass Mehdi⁴,Delorme Vincent¹⁵^ORCID,Djaout Kamel¹^ORCID,Trebosc Vincent⁶⁷,Kemmer Christian⁶,Wintjens René⁸^ORCID,Wohlkönig Alexandre⁹¹⁰^ORCID,Antoine Rudy¹,Huot Ludovic¹^ORCID,Hot David¹,Coscolla Mireia¹¹¹²,Feldmann Julia¹¹¹²^ORCID,Gagneux Sebastien¹¹¹²,Locht Camille¹,Brodin Priscille¹^ORCID,Gitzinger Marc⁶^ORCID,Déprez Benoit²^ORCID,Willand Nicolas²^ORCID,Baulard Alain R.¹^ORCID

Affiliation:

1. Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019-UMR8204-CIIL–Center for Infection and Immunity of Lille, F-59000 Lille, France.

2. Université Lille, Inserm, Institut Pasteur de Lille, U1177–Drugs and Molecules for Living Systems, F-59000 Lille, France.

3. Division of Translational Medicine and Chemical Biology, Science for Life Laboratory, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.

4. National Reference Center for Tuberculosis and Mycobacteria, Bacterial Diseases Service, Operational Direction Communicable and Infectious Diseases, Scientific Institute of Public Health (WIV-ISP), Brussels, Belgium.

5. Tuberculosis Research Laboratory, Institut Pasteur Korea, South Korea.

6. Bioversys AG, Hochbergerstrasse 60C, 4057 Basel, Switzerland.

7. Biozentrum, University of Basel, Basel, Switzerland.

8. Laboratoire des Biopolymères et des Nanomatériaux Supramoléculaires, Université Libre de Bruxelles, Brussels, Belgium.

9. VIB Center for Structural Biology, VIB, Pleinlaan 2, 1050 Brussels, Belgium.

10. Structural Biology Brussels, Vrije Universiteit Brussel (VUB), Pleinlaan 2, 1050 Brussels, Belgium.

11. Swiss Tropical and Public Health Institute, Basel, Switzerland.

12. University of Basel, Basel, Switzerland.

Abstract

Countering TB prodrug resistance The arsenal of antibiotics for treating tuberculosis (TB) contains many prodrugs, such as ethionamide, which need activation by normal metabolism to release their toxic effects. Ethionamide is potentiated by small molecules. Blondiaux et al. screened for more potent analogs and identified a lead compound called SMARt-420. This small molecule inactivates a TetR-like repressor, EthR2, and boosts ethionamide activation. SMARt-420 successfully promoted clearance of multidrug-resistant strains of Mycobacterium tuberculosis from the lungs of mice. Science , this issue p. 1206

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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