How bacteria resist fluoride

Fluoride anion is everywhere.  Released into water through the natural weathering of rocks, it’s present to the tune of 5 mM in toothpaste, 30 μM in Cape Cod bay, and 17 μM in Massell pond at Brandeis.

Fluoride levels in our environment (graph).001

Fluoride in the environment, measurements by Ashley Brammer (Miller lab)

Since F is ancient, ubiquitous and toxic to microbes, it’s not surprising that bacteria have evolved defenses to expel it from their cytoplasm.   In an article published in eLife on August 27, 2013, Randy Stockbridge, Janice Robertson, and Luci Partensky from Chris Miller’s lab describe one of these microbial defenses, a fluoride channel called Fluc.  The channel provides a pathway for F to exit the cell across the membrane at a rate of 107 ions per second, while rigorously excluding Cl in order to avoid catastrophic membrane depolarization. The world-record 10,000-fold selectivity isn’t the only remarkable aspect of Fluc, however. The Fluc channel is built on an antiparallel dimer scaffold, with one of the subunits facing the exterior of the cell, and the other facing the interior. Only one other modern-day membrane protein is known to dimerize like this, but the arrangement recalls the inverted structural repeats that are a common, important motif for membrane transporters. Inverted repeats are the product of an antiparallel dimer, like Fluc, that duplicated and fused eons ago.  The sequences drifted over time until the duplication was undetectable by sequence similarity, and the plethora of membrane transport proteins built on this plan was only discovered when the 3-D structures were solved. The Fluc family provides the opportunity to study microorganism resistance to an ancient xenobiotic, as well as membrane protein architecture from an evolutionary origin.

For more, you should read the paper:

Stockbridge RB, Robertson JL, Kolmakova-Partensky L, Miller C. A family of fluoride-specific ion channels with dual-topology architecture. eLife. 2013;2(0):e01084. PMCID: 3755343.

PS: If you’re wondering about the tea on the bar graph, tea plants accumulate F in their leaves.  Cheap teas, made from older tea leaves, actually carry a lot of F, and if you drink a couple quarts of lousy tea a day, you can give yourself skeletal fluorosis.

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