Title |
Reversion of antibiotic resistance in Mycobacterium tuberculosis by spiroisoxazoline SMARt-420
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Published in |
Science, March 2017
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DOI | 10.1126/science.aag1006 |
Pubmed ID | |
Authors |
Nicolas Blondiaux, Martin Moune, Matthieu Desroses, Rosangela Frita, Marion Flipo, Vanessa Mathys, Karine Soetaert, Mehdi Kiass, Vincent Delorme, Kamel Djaout, Vincent Trebosc, Christian Kemmer, René Wintjens, Alexandre Wohlkönig, Rudy Antoine, Ludovic Huot, David Hot, Mireia Coscolla, Julia Feldmann, Sebastien Gagneux, Camille Locht, Priscille Brodin, Marc Gitzinger, Benoit Déprez, Nicolas Willand, Alain R Baulard |
Abstract |
Antibiotic resistance is one of the biggest threats to human health globally. Alarmingly, multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis have now spread worldwide. Some key antituberculosis antibiotics are prodrugs, for which resistance mechanisms are mainly driven by mutations in the bacterial enzymatic pathway required for their bioactivation. We have developed drug-like molecules that activate a cryptic alternative bioactivation pathway of ethionamide in M. tuberculosis, circumventing the classic activation pathway in which resistance mutations have now been observed. The first-of-its-kind molecule, named SMARt-420 (Small Molecule Aborting Resistance), not only fully reverses ethionamide-acquired resistance and clears ethionamide-resistant infection in mice, it also increases the basal sensitivity of bacteria to ethionamide. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
France | 12 | 14% |
United Kingdom | 12 | 14% |
United States | 5 | 6% |
Netherlands | 3 | 3% |
India | 2 | 2% |
South Africa | 2 | 2% |
Spain | 2 | 2% |
Ireland | 2 | 2% |
Belgium | 1 | 1% |
Other | 10 | 12% |
Unknown | 35 | 41% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 51 | 59% |
Scientists | 28 | 33% |
Practitioners (doctors, other healthcare professionals) | 5 | 6% |
Science communicators (journalists, bloggers, editors) | 2 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 1% |
France | 1 | <1% |
Hungary | 1 | <1% |
Finland | 1 | <1% |
South Africa | 1 | <1% |
Unknown | 238 | 97% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 54 | 22% |
Researcher | 46 | 19% |
Student > Master | 26 | 11% |
Student > Bachelor | 24 | 10% |
Student > Postgraduate | 13 | 5% |
Other | 39 | 16% |
Unknown | 43 | 18% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 62 | 25% |
Agricultural and Biological Sciences | 43 | 18% |
Chemistry | 31 | 13% |
Immunology and Microbiology | 24 | 10% |
Medicine and Dentistry | 8 | 3% |
Other | 21 | 9% |
Unknown | 56 | 23% |