Weak acids permeation through (bio)membranes
Many (pathogenic) bacteria are auxotrophs and require subsets of nutrients for growth. To meet their requirements for these cellular building blocks, the bacteria use so-called ATP-Binding Cassette (ABC) transporters. Prokaryotic ABC transporters employ a substrate-binding protein (SBP) that captures the ligand and delivers it to the translocator for subsequent import into the cell. In E. coli these SBPs constitute 50-80% of all proteins in the periplasm. In collaboration with the group of Giovanni Maglia, we have devised a simple electrophysiology-based method to probe small molecule interference of substrate binding to SBPs trapped inside membrane-embedded pores. This method allows for rapid screening of large sets of molecules to inhibit essential transport processes in pathogenic bacteria and thus provide lead compounds for development of new antibiotics.
Department: GBB, RUG
Principal investigator(s): Prof. Bert Poolman
Publications
Gabba, M., Frallicciardi, J., van ’t Klooster, J., Henderson, R., Syga, Ł., Mans, R., van Maris, A. J. A., & Poolman, B. (2020). Weak Acid Permeation in Synthetic Lipid Vesicles and Across the Yeast Plasma Membrane. Biophysical Journal, 118(2), 422-434. https://doi.org/10.1016/j.bpj.2019.11.3384
Pols, T., Sikkema, H. R., Gaastra, B. F., Frallicciardi, J., Śmigiel, W. M., Singh, S., & Poolman, B. (2019). A synthetic metabolic network for physicochemical homeostasis. Nature Communications, 10(1), 4239. https://doi.org/10.1038/s41467-019-12287-2