Tuberculosis (TB) remains the world's deadliest infectious disease and a major public health challenge, particularly due to the emergence of multi-resistant and ultra-resistant strainsAmong the new therapeutic options, the pretomanid has recently received marketing authorization and is now used in combination with other antituberculosis drugs to treat resistant forms of the disease. However, its use has quickly been accompanied by the emergence of new resistances. In this context, the teams of Nicolas Willand (Drug Discovery Center, University of Lille – Inserm – Pasteur Institute of Lille) andAlain Baulard (CIIL, University of Lille, CNRS, Inserm, Pasteur Institute of Lille, Lille University Hospital) have identified small molecules capable of potentiating the activity of pretomanide on both susceptible and resistant strains. The researchers optimized the efficacy of these molecules and elucidated their mechanisms of action. These compounds target themycobacterial enzyme Rv2073c, a key player in bacterial cell wall biosynthesis. This inhibition blocks arabinane synthesis, leading to bacterial death. This work highlights Rv2073c as a critical vulnerability of Mycobacterium tuberculosis and pave the way for the development of new therapeutic strategies to enhance the effectiveness of antituberculosis treatments and fight against antibiotic resistance.
Exploiting DprE2 pathway redundancy to enhance potency and overcome resistance to pretomanid in Mycobacterium tuberculosis
Djaout K, Dreneau A, Faion L, Prieri M, Neuville M, Boulloy A, Biela A, Frita R, Devaere M, Slupek S, Antoine R, Hartkoorn RC, Vandeputte A, Piveteau C, Leroux F, Dumont-Ryckembusch J, Herledan A, Pál A, Záhorszká M, Mikušová K, Korduláková J, Guilhot C, Déprez B, Flipo M, Baulard A, Willand N.
NPJ Antimicrobial Resist. 2026 May 30. doi: 10.1038/s44259-026-00201-y
U1019 – UMR9017 “Lille Infection and Immunity Center” (University of Lille, CNRS, Inserm, Pasteur Institute of Lille, Lille University Hospital) / U1177 “Drug Discovery Center (University of Lille – Inserm – Pasteur Institute of Lille)
