Submitted by Yan Pan on Mon, 01/12/2025 - 15:14
New research led by the Universities of Cambridge and Basel shows how bacteria regulate membrane channels to control nutrient flow and antibiotic uptake, revealing a hidden mechanism of drug resistance.
A new study in Nature Microbiology, co-led by Professor Andres Floto at the Victor Phillip Dahdaleh Heart & Lung Research Institute, shows that bacteria can actively control what enters their cells, balancing nutrient intake with energy use, and reducing the effectiveness of some antibiotic treatments. The study reveals that bacterial porins, channels in the outer membrane, act like adjustable valves rather than always open holes.
Using single-cell imaging, ion sensing techniques, and experimental manipulation of periplasmic proton levels, the team showed that porin opening in Escherichia coli are regulated in response to internal proton (H⁺) and potassium (K⁺) concentrations. These ion levels fluctuate with the cell’s metabolic activity. A potassium channel, Kch, was found to play a key role in this process.
As first author Santiago Romero Canelón explains, “Many antibiotics enter through porins. Change permeability, change survival.” In their experiments, shifting metabolic states changed antibiotic sensitivity in line with porin permeability, showing that metabolism can influence how effectively drugs get inside bacterial cells.
These findings reveal a previously hidden mechanism by which bacteria can resist antibiotics. By adjusting porin permeability, they can reduce drug uptake while maintaining nutrient flow and energy balance. This membrane tuning may help explain why some infections are harder to treat. Understanding this process opens up new possibilities for improving antibiotic effectiveness, for example by targeting the ion regulated gating mechanism to force membranes open and allow better drug penetration.
The research was funded by the Wellcome Trust, UK Cystic Fibrosis Trust, LifeArc, National Institute for Health and Care Research Cambridge Biomedical Research Centre, Fondation Botnar, University of Cambridge, Engineering & Physical Sciences Research Council, and Biotechnology and Biological Sciences Research Council.
Reference
Caño Muñiz, S.E., Trigg, S., Hardo, G. et al. Metabolic control of porin permeability influences antibiotic resistance in Escherichia coli. Nat Microbiol (2025). https://doi.org/10.1038/s41564-025-02175-5
