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Bromine found to be essential to animal life

Fruit flies deprived of the element die as larvae

FULL OF HOLES  Basement membranes help maintain tissues (fruit fly gut, left) in animals. Fruit flies raised without bromine (middle) develop holes (red arrows) in the basement membrane that can be repaired by adding bromine to the diet (right). Scale bar represents 20 micrometers.

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Bromine is a secret ingredient in the recipe for animal life. The element is necessary for helping cells in multicellular animals stick together, researchers report in the June 5 Cell.

Previously, scientists knew that animals had bromine in their bodies, but researchers could find no biological use for it.

“The bottom line is of 92 naturally occurring elements, 27 are essential for the animal kingdom,” says Billy Hudson, a biochemist at Vanderbilt University in Nashville who led the work. At least, that was the number before the new study. “Now there are 28.”

Hudson’s team found that Drosophila melanogaster fruit flies need bromine to live. The researchers also provided insight into why bromine is essential for all animals, says Kevin Campbell, a membrane biologist at the University of Iowa in Iowa City.

Bromide ions, negatively charged versions of bromine, stabilize cellular support structures called basement membranes, Hudson’s team found. Basement membranes are connective tissue outside cells. Basement membranes are composed of ropes of collagen and other large molecules. The external scaffold helps give cells their shapes.

Bromide facilitates formation of a chemical bond that lashes ropes of one type of collagen together. Hudson’s team reported last year that these bonds — sulfur-nitrogen bonds called sulfilimine bonds — are necessary for multicellular animals (SN Online: 12/17/13). The researchers had also previously discovered that an enzyme called peroxidasin forges those bonds. In the new study, the researchers found that the enzyme needs bromide ions to function properly.

Other closely related elements, such as chlorine, might be able to substitute for bromine, though. To determine whether bromine is essential, the researchers eliminated it from the fruit flies’ diet. That’s no easy task, says coauthor Christopher Cummings, a Vanderbilt biochemist: “It’s in the environment everywhere.”

Even the tiny amounts of bromine that contaminate laboratory stocks of sodium chloride were enough to throw off experiments, Cummings says. The researchers had to purify their own chloride supply, needed to grow the yeast that flies eat and make the reagents used to study the peroxidasin’s activity, to rid it of bromide.

The team fed female fruit flies a regular or bromine-free diet and tracked what happened to the flies’ offspring. More than half of eggs from mothers fed a regular diet hatched, but only about 20 percent of eggs from bromine-free females did. Of the bromine-free larvae that did hatch, almost none survived to adulthood. Closer examination revealed that the basement membranes in bromine-free larvae were abnormal and the guts of the flies did not develop properly as a result. When the researchers restored bromine to the larvae’s diet, the insects grew into normal adults.

Being able to reverse the fruit flies’ fate shows that sound basement membranes are crucial to animal life, says Kaustabh Ghosh, a vascular biologist at the University of California, Riverside, who studies how cells use mechanical forces to communicate with each other. The finding adds to growing evidence that the scaffolding outside cells isn’t just a passive support structure; it provides cues about how cells should behave. Cells in contact with abnormal basement membranes may become cancerous, previous studies have shown (SN: 10/5/13, p. 20).

The researchers’ demonstration that bromine’s role in forming the basement membrane is necessary for life could be important for human health too, Ghosh says. “The implications are far-reaching,” he says, adding that currently, “it doesn’t raise much of an alarm if you’re low in bromine. This says you should take it seriously.”

Although people usually get plenty of bromine in normal diets, people undergoing dialysis or getting their nutrients intravenously sometimes have low levels of the element in their blood, previous studies have shown. Hudson’s team plans to investigate whether that deficiency might cause medical problems and whether bromine supplements could help.

The team also discovered that a chemical in tobacco smoke called thiocyanate inhibits peroxidasin’s reaction. That might mimic a bromine deficiency in smokers and help explain why basement membranes in their lungs start to break down.  

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