As part of the ISIDORe project, Joana Santos from i3S (Portugal) collaborated with Instruct-ERIC’s Membrane Protein Production Lab at Diamond Light Source (UK) to advance our understanding of drug resistance in Mycobacterium tuberculosis (Mtb). This bacterium, responsible for over a million deaths each year, has developed multidrug-resistant strains through mechanisms like efflux pumps that expel antibiotics from the cell.
To support the development of novel inhibitors targeting these pumps, the team screened five mycobacterial efflux pumps using a high-throughput membrane protein expression platform. Although bacterial expression systems were unsuccessful, mammalian cell expression yielded high-quality material. Three pumps were prioritized for further analysis, and one produced promising early structural data via Cryo-EM.
This structural and biochemical work lays the groundwork for designing drugs that could reinstate the efficacy of existing TB treatments. Future steps will deepen characterization using transport assays and high-resolution techniques, with results intended for wide dissemination in open-access formats and scientific forums.