Fluoride ion (F−) is a ubiquitous environmental threat to microorganisms, which have evolved a family of highly selective “Fluc” F− channels that export this inhibitory anion from their cytoplasm. It is unclear, however, how a thermodynamically passive mechanism like an ion channel can protect against high concentrations of external F−. We monitored external F− concentrations in Escherichia coli suspensions and showed that, in bacteria lacking Fluc, F− accumulates when the external medium is acidified, as a predicted function of the transmembrane pH gradient. This weak acid accumulation effect, which results from the high pKa (3.4) and membrane permeability of HF, is abolished by Fluc channels. We also found that, although bacterial growth is inhibited by high concentrations of F−, bacteria can withstand cytoplasmic F− at levels a hundred times higher than those that inhibit proliferation, resuming growth when the F− challenge is removed.
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