| Description: |
Porins mediate the passage of hydrophilic nutrients and antibiotics across the outer membrane but might contribute to proton leak from the periplasm, suggesting that their conductance could be regulated. Here we show, using single-cell imaging, that porin permeability in Escherichia coli is controlled by changes in periplasmic H+ and K+ concentration. Conductance through porins increases with low periplasmic H+ caused by starvation, promoting nutrient uptake, and decreases with periplasmic acidification during growth in lipid media, limiting proton loss. High metabolic activity during growth in glucose media, however, activates the inner membrane voltage-gated potassium channel, Kch, increasing periplasmic potassium and enhancing porin permeability to dissipate reactive oxygen species. This metabolic control of porin permeability explains the observed increase in ciprofloxacin resistance of bacteria catabolizing lipids and clarifies the impact of mutations in central metabolism genes on drug resistance, identifying Kch as a therapeutic target to improve bacterial killing by antibiotics. ; Supported by Wellcome Trust grants Investigator award 107032AIA (R.A.F., S.E.C.M, A.H., I.E.E.) and Discovery award 226602/Z/22/Z (R.A.F, ST, AH, CR, FC-W), the UK Cystic Fibrosis Trust Innovation Hub grant 001 (S.E.C.M, A.H., T.L.B., R.A.F.); LifeArc/CF Trust Innovation Hub THUB01 (R.A.F, ST, AH, CR, FC-W) as part of the Translational Innovation Hub Network for CF Lung Health & Infection; the NIHR Cambridge Biomedical Research Centre (R.A.F.); Botnar Foundation grant 6063 (S.E.C.M., R.A.F., T.L.B) |