Scientists have figured out why microbes can flourish in super toxic, fluoride-rich environments.
The secret is an unusual ion channel that exports fluoride from the cell, according to a new study published in the journal eLife.
The discovery may have implications for treating bacterial diseases such as tuberculosis, say Brandeis University scientists.
Ions are electrically charged molecules that need help from one of two types of membrane transport proteins—carriers and channels—to cross cell membranes.
Carriers act like taxis, ferrying ions into and out of the cell. Channel proteins are more like one-way tunnels, forming a pore in the cell membrane that transports ions from areas of high concentration to areas of low concentration.
Upside down and backwards
Fluoride ions are sneaky. They seep into cells in protonated form—as hydrofluoric acid—and when the acid breaks down in the cell’s higher pH, only the fluoride ions remain. Since hydrofluoric acid is easily able to permeate cell membranes, cells accumulate fluoride at higher levels than their extracellular environments.
That accumulation activates a family of transport proteins, called Fluc, to build a channel so specific that it can distinguish between the harmful fluoride and the closely related but harmless chloride, making it the most selective channel yet discovered.
The channel is also unusual in that its structure is upside down and backwards from every other channel protein studied.
“This newly discovered ion channel violates all the rules of known channels,” says Christopher Miller, professor of biochemistry.
In examining how this channel works, Miller and his team disabled a microbe’s internal security system by using a bacterial strain whose Fluc gene is knocked out.
When these bugs are exposed to fluoride, the ion accumulates and inhibits the production of energy by glycolysis and the synthesis of DNA and RNA. The scientists could then replace the Fluc gene, or similar genes from other organisms, to rescue the bacteria from this hypersensitivity to fluoride.
Since fluoride is mostly non-toxic to humans (but don’t eat your toothpaste), this strategy may be one avenue to explore in developing treatments for harmful bacterial diseases, Miller says. But for the moment, the channel’s weird, wild structure is captivating enough.
Source: Brandeis University