Ever since the FDA approved the drug bedaquiline, which interferes with the bioenergetics of Mycobacterium tuberculosis by inhibiting the activity the F0F1-ATP synthase, respiratory-chain enzymes have been an active target space for the discovery of new antibiotics. To aid in this pursuit, we aim to gain a deeper understanding of key respiratory enzymes in bacterial pathogens.

M. tuberculosis, the causing pathogen of tuberculosis (TB), has two different enzymes to respiration on oxygen: cytochrome bc₁:aa₃ and cytochrome bd. When both are inhibited, pathogenicity of M. tuberculosis is significantly perturbed.  Although inhibitors of cytochrome bd are known, it is currently unknown what their mechanism of action is. We study cytochrome bd from M. tuberculosis and Escherichia coli to understand how these inhibitors work and help develop antibiotics in the future.

Listeria monocytogenes is a food-born pathogen, able to grow at both low and high temperatures, and causes a serious food poisoning called listeriosis even from properly refrigerated foods. Under anaerobic conditions, L. monocytogenes transfers electrons out of the cell to redox balance its fermentative metabolism. It has been shown that this extracellular electron transport (EET) is required for survival and virulence of L. monocytogenes. In collaboration with Prof. D. Slotboom from University Groningen, we are studying the proteins involved in EET from L. monocytogenes as a promising target space for new antibiotics.

Key publications

Velden T.T. van der, Kayastha K., Waterham C.Y.J., Brünle S. & Jeuken L.J.C. (2025), Menaquinone-specific turnover by Mycobacterium tuberculosis cytochrome bd is redox regulated by the Q-loop disulfide bond, Journal of Biological Chemistry 301(2): 108094. DOI: 10.1016/j.jbc.2024.108094

Nakatani Y., Shimaki Y., Dutta D., Muench S.P., Ireton K., Cook G.M. & Jeuken L.J.C. (2019), Unprecedented Properties of Phenothiazines Unraveled by a NDH-2 Bioelectrochemical Assay Platform, Journal of the American Chemical Society 142: 1311-1320. DOI: 10.1021/jacs.9b10254