Electrochemical coupling of porin permeability and metabolism controls antibiotic resistance in bacteria

Abstract

Bacterial porins permit permeation of hydrophilic nutrients and antibiotics across their outer membrane but might also contribute to proton leak from the periplasmic space, suggesting that their conductance could be regulated. Here we show that, in Escherichia coli, porin permeability is controlled by changes in periplasmic H+ and K+ concentrations. Conductance through porins is increased by low periplasmic H+ caused by starvation, promoting nutrient uptake, and decreased by periplasmic acidification during growth in lipid media, thereby limiting proton loss during electron transport chain activity. In contrast, high metabolic activity, seen during growth in glucose media, activates the inner membrane voltage-gated potassium channel, Kch, increasing periplasmic potassium levels and enhancing porin permeability to dissipate reactive oxygen species (ROS). This metabolic control of porin permeability explains, at least in part, the recognised decrease in ciprofloxacin susceptibility when bacteria utilise lipid carbon sources, and the impact of mutations in central metabolism genes on drug resistance, identifying Kch as a therapeutic target to improve bacterial killing by antibiotics

Recommended citation: Muniz, Santiago Cano., et al. (2022). "Ionic control of porin permeability in bacteria." bioRxiv