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Nutrient gradients in biofilms cause bacteria to organize into metabolically versatile communities capable of withstanding threats from external agents including bacteriophages, phagocytes, and antibiotics. We previously determined that oxygen availability spatially organizes respiration in uropathogenic  Escherichia coli  biofilms, and that the high-affinity respiratory quinol oxidase cytochrome  bd  is necessary for extracellular matrix production and biofilm development. In this study we investigate the physiologic consequences of cytochrome  bd  deficiency in biofilms and determine that loss of cytochrome  bd  induces a biofilm-specific increase in expression of general diffusion porins, leading to elevated outer membrane permeability. In addition, loss of cytochrome  bd  impedes the proton mediated efflux of noxious chemicals by diminishing respiratory flux. As a result, loss of cytochrome  bd  enhances cellular accumulation of noxious chemicals and increases biofilm susceptibility to antibiotics. These results identify an undescribed link between  E. coli  biofilm respiration and stress tolerance, while suggesting the possibility of inhibiting cytochrome  bd  as an antibiofilm therapeutic approach.

Cytochrome bd promotes Escherichia coli biofilm antibiotic tolerance by regulating accumulation of noxious chemicals