DEciphering The mOde of action of powerful New AntiTuberculOsis dRugs – DETONATOR
The emergence of antimicrobial resistance among tuberculosis (TB) harshly impairs TB control. Fluoroquinolones (TB) are one of the core antibiotics used to treat MDR-TB. Analysis of structure activity relationship among a series of lipophilic analogues of FQ recently synthesized revealed 2 molecules (HIT18 and 19) that remain fully active against clinical strains resistant to FQ. These data strongly suggest that these HITs have acquired a mode of action different than the one of standard FQ, implicating an uncharacterized TB protein. Therefore, in the particular context of crucial need of new anti-tuberculous drugs, we set up a consortium of highly experienced research teams that will address the mode of action, the evasion mechanisms, and the optimization of the structure and activity of this promising new class of molecules through a multidisciplinary approach merging pharmacology, microbiology, fluorescence microscopy, genomic, proteomic, and biochemical studies.
Madame Alexandra Aubry (Centre d'Immunologie et de Maladies Infectieuses)
The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.
IPL - U1177 Institut Pasteur de Lille - M2SV : Médicaments et Molécules pour Agir sur les Systèmes Vivants
LINNAEUS BIOSCIENCE / Linnaeus
IPL - CIIL Institut Pasteur de Lille - Centre d'Infection et d'Immunité de Lille
CIMI Centre d'Immunologie et de Maladies Infectieuses
Help of the ANR 559,321 euros
Beginning and duration of the scientific project: May 2021 - 42 Months