Fluoride: unless you’re a synthetic chemist or a dentist, you probably don’t worry about this ion very often.  But, according to a new paper published in Science, bacteria do, and have done for a very long time.

The work, spearheaded by Ron Breaker’s group at Yale University, identified a novel RNA motif that selectively binds fluoride ion.  In response to F^– binding, this motif, called a riboswitch, undergoes a structural change that leads to increased transcription of downstream genes.  These genes encode crucial metabolic enzymes that are strongly inhibited by fluoride ion, like enolase and pyrophosphatase, as well as members of a family of chloride transport proteins, the CLC’s.  The CLC’s that are associated with F^– riboswitches are clustered together in a phylogenetic clade distant from well-characterized CLC’s.  Could these “chloride” channel proteins actually assist with fluoride export?  Randy Stockbridge, a Brandeis postdoc working in Chris Miller’s lab, contributed to the findings by showing that this subset of riboswitch-associated CLC’s do, in fact, transport F^–, whereas “conventional” CLC’s strictly exclude F^–.   The F^– riboswitches, and the F^– CLC’s, are found among a huge variety of bacteria and archaea, from plant and human pathogens to benign soil and seawater-dwelling bugs, leading to the inference that F^– toxicity has been a consistent evolutionary pressure.

You’re probably wondering just how much fluoride there is in the environment.  Fluoridated municipal drinking water contains about 80 micromolar F^–, and natural F- concentrations in the environment can be  higher and lower than that number.   In acidic environments especially, F^– might accumulate to much higher levels in bacteria.  With a pK_a of 3.4, a small amount of F^– is present as HF at low pH, and the uncharged HF can diffuse cross the cell membrane into the cell.  Once in the cytoplasm, where the pH is around 7, HF dissociates, and F^– can’t diffuse across the membrane back into the environment.  Unless, of course, evolution has provided that bacterium a system to transport F^– out of the cell…

see also

• Yale news story on how the Breaker lab figured out it was fluoride that bound to these riboswitches
• Baker JL, Sudarsan N, Weinberg Z, Roth A, Stockbridge RB, Breaker RR. (2012). Widespread genetic switches and toxicity resistance proteins for fluoride.  Science.  335: 233-235.