May Offer Target for Antibiotic Design and Insights Into Evolution of Life
Oxygen is poison to some disease-causing bacteria. For years, scientists have wondered how bacteria that grow in the absence of oxygen (called “anaerobes”) are able to sense oxygen in their environment and swim away from it to avoid death. Now, they have identified an unusual protein that may explain how they do this. The protein could also offer a potential target for the design of new antibiotics and provide insight into the evolution of life, they say.
The finding is described in the May 16 issue of Biochemistry, a peer-reviewed journal of the American Chemical Society, the world’s largest scientific society.
“We propose that, since this bacterium is poisoned by air, [the protein’s] oxygen-binding domain senses when oxygen is present in the environment and causes the bacteria to swim away from it,” says Donald M. Kurtz, Jr., Ph.D., the principal investigator of the study and a professor of chemistry at the University of Georgia, located in Athens, Ga.
He continues, “We suspect that this system may be a general oxygen-sensor in anaerobic microorganisms.”
Some anaerobic bacteria can cause human diseases such as gingivitis (gum disease) and gangrene. If Kurtz is correct, his finding could lead to development of new antibiotics.
Since the initial finding, the researchers have identified similar proteins in 12 different bacteria, evenly distributed between anaerobic and aerobic (able to use oxygen). Although many disease-causing bacteria are aerobic, some are able to grow anaerobically as well. If they, too, contain this protein, they could also be vulnerable to drugs that inactivate it, says Kurtz.
Such drugs could provide a new weapon to fight the growing problem of antibiotic resistance, in which bacteria that are normally killed by drugs become resistant to them, he says.
The researchers made their initial discovery while searching gene and protein databases, where they observed a DNA sequence encoding a previously unrecognized oxygen-binding protein in an anaerobic bacterium. This protein closely matched one that had previously been found only in a small group of marine organisms, including a species of worm (called “peanut worms”) that live in the tidal flats of oceans. Until now, researchers had wondered why this protein was found only in this small group of marine organisms and not others.
The tidal flats where the worms live are a mostly anaerobic environment. However, unlike the anaerobic bacterium studied, the worms do not actively avoid oxygen and are not killed by it.
Researchers now believe that the protein has different functions in the two organisms, all related to their ability to detect oxygen. In the bacterium, the protein is for sensing and avoiding oxygen. In the worm, the protein appears to serve as an oxygen-storage reserve, providing oxygen whenever the worm needs it, says Kurtz.
This finding has evolutionary implications. “I’m suggesting that the bacteria developed the protein originally and that the worm sort of adapted it to do something different,” says Kurtz.
The evolution of an oxygen-sensing protein was probably a matter of survival, he theorizes. Most scientists believe that the Earth’s original atmosphere was devoid of oxygen and that, consequently, the first organisms to evolve were anaerobic. In this environment, the earliest bacteria probably did not need any structures to help them avoid oxygen because it was not a danger, the researcher says.
As the Earth evolved, plants emerged that steadily produced oxygen. The anaerobic bacteria had to either adapt or die in the new oxygen-rich atmosphere. That’s when the bacteria began to evolve oxygen-sensing proteins, which were eventually incorporated by other organisms, Kurtz theorizes.
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