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Single-celled organisms from ocean’s depths reveal genetic breakthrough, medical potential

by
Scope Correspondent

Miles beneath the surface of the Pacific Ocean, in cold, pressure, and complete darkness, Earth rips and folds along its seams. Seawater meets molten rock, and shoots upward as a superheated, chemical-laden soup. These are hydrothermal vents, the planet’s underwater volcanoes. Their bizarre world, full of strange creatures and extreme conditions, might seem like the last place to discover broadly applicable scientific breakthroughs. But the smallest organisms from this world, and the unexplored oceans at large, might hold profound insight for our own. Researchers have revealed that one hydrothermal vent microbe contains genetic material seen all over the world, and could help humans fight disease.

Meet Aciduliprofundum boonei, the species behind this discovery. A. boonei is an archaeon, a single-celled organism that somewhat resembles a bacterium in structure but is genetically quite different. On November 25, 2014, a study published in the journal eLife revealed that A. boonei contains a gene encoding an enzyme that can break bacterial cell walls.

This enzyme could be a powerful tool for human medicine. It’s been shown to kill disease-causing bacteria, and could someday be used as an antibiotic. Seth Bordenstein, Associate Professor of Biology at Vanderbilt University and an author of the new study, wrote in a November 26 email that Vanderbilt is looking for industry partners to pursue this possibility.

It’s an excellent example of how nature can be the best source of inspiration for new medicines. Natural molecules evolve to have some useful biological property, and if a researcher can understand how those molecules work in biological systems, “we can take advantage of that in therapeutic ways,” says William Gerwick, professor of Oceanography and Pharmaceutical Sciences at the Scripps Institution of Oceanography and University of California, San Diego, who was not involved with the study.

It seems that A. boonei uses the enzyme as an antibacterial agent, too. Both bacteria and archaea thrive on the porous rocks and abundant geochemicals at hydrothermal vents. “They love it because they’re basically sitting in a Jacuzzi,” says Anna-Louise Reysenbach, a professor of biology at Portland State University and an author of the new study. Ultimately, the microbes have to compete for space and resources—and a bacterial-splitting enzyme becomes a useful weapon in this battle. When researchers grew A. boonei along with bacteria from their natural habitat, the archaea’s enzyme-coding gene became more active, and bacterial growth was limited. The enzyme could also help archaea obtain food, says Reysenbach. Archaea love to eat proteins, which live bacteria contain; with this enzyme, A. boonei could turn a nearby bacterium into a protein piñata.

If humans turn this enzyme into a successful antibiotic, it would represent a second iteration of biological hijacking. Genetic analyses show that A. boonei actually took their enzyme-producing gene from bacteria. Bacteria normally use the produced enzyme to divide in half during reproduction; the archaea have turned it into an antibacterial weapon, just as humans might.

This genetic swapping is known as horizontal gene transfer. Bordenstein describes it as “the interesting process in which genes ‘jump’ from one organism’s genome into an unrelated genome.” It’s pretty common between different species of bacteria, Bordenstein says. It happens in other organisms, too—for example, aphids have stolen from fungi. But this study is particularly surprising. Researchers found the genetic code for this enzyme in not only bacteria and archaea, but also a plant, an insect, and a fungus often used in Japanese cooking.

This is significant because it represents gene transfer across all major divisions of life. In the broadest genetic sense, there are three “domains” of organisms—Bacteria, Archaea, and Eukarya (which includes all plants, animals, fungi, and protists like yeast). Horizontal gene transfer has been shown to span two different domains of life before, Bordenstein says, but seeing it across all three is “unprecedented.”

Horizontal gene transfer can be an extremely useful evolutionary trick. Organisms can use beneficial genes from other species to survive sudden changes in their environments, writes Marleen van Wolferen, a postdoctoral researcher at Albert Ludwigs University of Freiburg who was not involved with the study. It can also enable species to spread to new environments, van Wolferen says. This enzyme gene had been slightly “retooled” in each organism, pairing with different genes for a different outcome. “The significance here is that evolution is opportunistic,” Bordenstein writes. Bacteria use the product of the gene for reproduction; fungi may use it for digestion; in other organisms, it’s antibacterial.

The spread of an antibacterial trait is actually an encouraging counterpoint to another common result of horizontal gene transfer: antibiotic resistance. Lateral gene transfer of drug-resistant genes is believed to be a primary cause in the rise of antibiotic resistant bacteria, which kill 23,000 Americans every year. This study shows that “not only do the antibacterial resistance genes move around, but the genes that are capable of attenuating growth of other bacteria are also capable of spreading,” says Anthony Poole, an associate professor in Biological Sciences at the University of Canterbury who was not involved with the study.

The medical potential of A. boonei’s acquisition may make humans the next species to benefit, though indirectly, from this gene transfer. A. boonei may be particularly well-suited to drug development: because it naturally thrives in a hot environment, it’s likely that any compounds it produces would be stable in the warm human body. But archaea at large may have a lot more to offer medicine, as well. Bordestein believes the domain “may represent an untapped source for antibiotic therapeutics.” Poole agrees. Many researchers have written off archaea when studying medically important microbes, he says. “What this paper does is give us a wake up call that we should be embracing the diversity of life while we’re asking those questions.”

And it seems the oceans may be the best place to search for new drugs. “We looked to natural products from the terrestrial world for many years, and it has yielded many exciting compounds…but the marine world has been relatively little explored to date,” Gerwick says. He also emphasizes the role that microbes like archaea and bacteria might play in this exploration. “I think that the last maybe fifteen to twenty years has really opened our eyes to the fact that the real treasures that are present in the marine environment are coming from its microbial life.”

Reysenbach agrees that massive potential remains beneath the sea—especially far, far beneath the surface. Every time she goes to a new hydrothermal vent site, she discovers a new species, she says. Eight years ago, it was a heat and acid-loving archaeon her team named A. boonei—an organism that has quickly proven its evolutionary and medical relevance. “The most explored areas are soils of the world, and we have only studied a minute part of the deep oceans,” Reysenbach says. “And so this little study shows that from one little discovery, the potential is huge.”

 

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