Dr. Alexandra Aubry - Fighting resistance to antibiotic against mycobacteria: how can bench and bedside combine their forces?

Alexandra Aubry

Faculté de Médecine Sorbonne Université, Assistance Publique-Hôpitaux de Paris (France)

Fighting resistance to antibiotic against mycobacteria: how can bench and bedside combine their forces?

Through the example of drug resistance in tuberculosis (TB), we will see how fighting resistance needs combined efforts from "bench" (e.g. developing molecular methods to diagnose resistance) and bedside. We will focus on fluoroquinolones (FQ) are key antibiotics against M. tuberculosis, the causative agent of tuberculosis. Studying the mechanisms of resistance to FQ in TB led to (i) refine molecular but also phenotypic methods enabling to diagnose antibiotic resistance in TB; (ii) illustrate how preclinical murine model are of great value to decipher the impact of mutations responsible for various level of resistance; (iii) translate to personalized treatment for TB patients. Alexandra Aubry will also give an overview of the ongoing area of research studied in her group at the Cimi-Paris.

Selected references

1. A. Aubry, X.S Pan, L.M. Fisher, V. Jarlier, E. Cambau. Mycobacterium tuberculosis DNA gyrase: interaction with quinolones and correlation with antimycobacterial drug activity. Antimicrob. Agents Chemother. 2004 ; 48 (4) : 1281-8
2. A. Bouige, A. Darmon, J. Piton, M. Roué, S. Petrella, E. Capton, P. Forterre, A. Aubry*, Mayer C*. The Mycobacterium tuberculosis DNA gyrase possesses two functional GyrA-boxes. Biochem J. 2013; 455(3) : 285-94
3. A. Pantel, S. Petrella, N. Veziris, S. Matrat, A. Bouige, H. Ferrand, W. Sougakoff, C. Mayer, A. Aubry. Description of compensatory gyrA mutations restoring fluoroquinolone susceptibility in Mycobacterium tuberculosis. Journal of Antimicrobial Chemotherapy. 2016 ; Sep;71(9):2428-31
4. S. Petrella, E. Capton, B. Raynal, C. Giffard, A. Thureau, F. Bonneté, P. M. Alzari, A. Aubry*, C. Mayer*. Overall structures of Mycobacterium tuberculosis DNA gyrase reveal the role of a Corynebacteriales GyrB specific insert in ATPase activity. Structure. 2019 Apr 2;27(4):579-589.e5
5. Godmer A, Bigey L, Giai-Gianetto Q, Pierrat G, Mohammad N, Mougari F, Piarroux R, Veziris N, Aubry A. Contribution of machine learning for subspecies identification from Mycobacterium abscessus with MALDI-TOF MS in solid and liquid media. Microb Biotechnol. 2024 Sep;17(9):e14545

The organization of this seminar is supported by the B2S Federation.