Fluoride resistance in the oral microbiome

The oral microbiome is composed of bad microbes that cause tooth decay and oral disease and good microbes that promote oral health. Remarkably, the good oral bacteria resist fluoride using different export proteins than disease-causing bacteria and yeasts. We’re interested in learning more about how fluoride exposure and resistance alters the oral biofilm ecology, the structures and mechanisms of fluoride export proteins in oral yeasts, and whether we can exploit differences in fluoride export mechanism to develop selective oral antimicrobials to treat dental diseases.

Oral pathogen S. mutans resists fluoride using F-/H+ antiporters known as CLCFs. In contrast, oral streptococci associated with health resist fluoride using fluoride channels known as Flucs. Eukaryotic species, including pathogenic yeasts like C. albicans, export fluoride using a third type of export protein called FEX.

For several years, we have studied the structures and mechanisms of these proteins. These studies have given us detailed molecular information about how fluoride exporters work, and provide a strong foundation for these studies.

*This collage shows a Fluc crystal, the protein’s ion permeation pathway (with fluoride ions in pink) and an electrophysiological recording of a single Fluc channel opening and closing.*

Here are a selection of articles from our lab about fluoride export:

Banerjee A, Kang C-Y, An M, Koff BB, Sunder S, Kumar A, Tenuta LMA, Stockbridge RB. (2024). Fluoride export is required for competitive fitness of pathogenic microorganisms in dental biofilm models. mBio. 0:e00184-24

McIlwain BM, Ruprecht MT, Stockbridge RB. (2021). Membrane exporters of fluoride ion. Annual Review of Biochemistry. 90:559-579.

McIlwain BM, Gundepudi R, Koff BB, Stockbridge RB. (2021). The fluoride permeation pathway and anion recognition in Fluc family fluoride channels. eLife 10e69482.

Stockbridge RB, Kolmakova-Partensky L, Shane T, Koide A, Koide S, Miller C, Newstead S. (2015). Crystal structures of a dual-topology, double-barrelled fluoride ion channel. Nature. 525:548-551. Learn about the structure in this article!

Stockbridge RB, Robertson JL, Kolmakova-Partensky L, Miller C. (2013). A family of fluoride- specific ion channels with dual-topology architecture. eLife 2013;2:e01084. Read about the characterization of fluoride channels here!

Stockbridge RB, Lim H-H, Otten R, Williams C, Shane T, Weinberg Z, Miller C. (2012). Fluoride resistance and transport by riboswitch-controlled CLC antiporters. Proc. Natl. Acad. Sci. U.S.A. 109: 15289-15294. Read the article here!