SCIENCE@home

Metabolic control of porin permeability influences antibiotic resistance in Escherichia coli

Santiago E. Caño Muñiz,Stephen Trigg,Georgeos Hardo,Anja Hagting,Ieuan E. Evans,Christopher Ruis,Ali F. Alsulami,David Summers,Felicity Crawshay-Williams,Tom L. Blundell,Lucas Boeck,Somenath Bakshi,R. A. Floto

Published 2025 in Nature Microbiology

ABSTRACT

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. The permeability of bacterial porins is dynamically regulated by periplasmic proton and potassium concentrations, altering antibiotic resistance.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-93 of 93 references · Page 1 of 1

CITED BY