Pathology professor developed a synthetic compound based on the mighty microbe that could lead to new forms of protection from deadly radiation
Researchers at Uniformed Services University of the Health Sciences (USU) and Northwestern University (NWU) have discovered the secret behind the ability of Deinococcus radiodurans (D. radiodurans)—a microbe dubbed “Conan the Bacterium”—to withstand levels of ionizing radiation that would kill other organisms, according to an NWU news release. The discovery may lead to new forms of protection from radiation exposure and also have applications in vaccine development.
The research also could provide new opportunities for clinical laboratories to be involved in diagnosing patients’ conditions and help guide selection of appropriate radiation therapies.
The protection comes not from D. radiodurans itself, but from a synthetic antioxidant called melatonin-derived protective (MDP) developed by Michael Daly, PhD, a professor in USU School of Medicine’s Department of Pathology who was inspired by chemistry within the microbe, according to the news release.
“It is this ternary complex that is MDP’s superb shield against the effects of radiation,” said Brian Hoffman, PhD, in the press release. Hoffman, a professor of chemistry at NWU, worked with Daly on the research.
The secret, the two scientists discovered, lies in the combination of three components: phosphate and a designed synthetic peptide known as DP1 which are bound to manganese.
The researchers published their findings titled, “The Ternary Complex of Mn2+, Synthetic Decapeptide DP1 (DEHGTAVMLK), and Orthophosphate Is a Superb Antioxidant,” in the journal Proceedings of the National Academy of Sciences (PNAS).
“We’ve long known that manganese ions and phosphate together make a strong antioxidant, but discovering and understanding the ‘magic’ potency provided by the addition of the third component is a breakthrough,” said Brian Hoffman, PhD (above), Professor of Molecular Biosciences at Northwestern University. “This study has provided the key to understanding why this combination is such a powerful—and promising—radioprotectant.” Continuing research in this area might give clinical laboratories new opportunities to screen patients for vaccines and radiation treatments. (Photo copyright: Northwestern University.)
Surviving on Mars
The new research built on a 2022 study, also led by Daly and Hoffman, in which the scientists tried to determine how long D. radiodurans and other microorganisms could survive on Mars when dried and frozen. As noted in an earlier NWU press release, the planet “is constantly bombarded by intense galactic cosmic radiation and solar protons.”
They subjected the microbes to the same cold and arid conditions present on Mars and exposed the organisms to varying levels of radiation. The researchers determined that if deeply buried, D. radiodurans could survive for more than 280 million years and withstand 140,000 grays of radiation. “This dose is 28,000 times greater than what would kill a human,” the press release notes.
Using an advanced spectroscopy technique, the researchers measured the levels of manganese antioxidants within the microorganisms. They determined that higher amounts of the antioxidants increased resistance to radiation.
Fabricating MDP
Daly describes MDP as “a simple, cost-effective, nontoxic and highly effective radioprotector,” according to Live Science.
“Ionizing radiation—such as X-rays, gamma rays, solar protons and galactic cosmic radiation—is highly toxic to both bacteria and humans,” Daly, told Live Science, adding, “In bacteria, radiation can cause DNA damage, protein oxidation, and membrane disruption, leading to cell death. In humans, radiation exposure can result in acute radiation syndrome, increased cancer risk, and damage to tissues and organs.”
Manganese is part of a complex within the microbes that removes the free radicals, Live Science explained.
Daly’s team designed a “lab-made version” of this mechanism by combining manganese and phosphate ions with a synthetic peptide that is similar to amino acids within the microbe.
In the new study, the researchers used a technique known as advanced paramagnetic resonance spectroscopy to characterize MDP, revealing the ternary complex as the “active ingredient” that gives it protective powers.
Real-world Applications for MDP
Daly described some potential applications of their discovery.
“Astronauts on deep-space missions are exposed to chronic high-level ionizing radiation, primarily from cosmic rays and solar protons,” he told Live Science, suggesting that MDP “could be administered orally to mitigate these space radiation risks.”
He added that MDP could also be used as a form of prevention against acute radiation syndrome. “There’s also a well-recognized link between radiation resistance and aging,” he said.
The technology could also lead to new radiation-inactivated vaccines, the latest NWU press release notes.
A team of scientists at USU employed MDP to develop an experimental vaccine that could help prevent chlamydia infection, according to a USU press release. The technology enabled researchers to inactivate the bacterium with radiation while protecting the proteins needed to stimulate immune response.
“If you want an effective whole-cell chlamydia vaccine, then you should probably try not to cook, zap, or otherwise damage the surface antigens that it relies on,” said USU researcher and assistant professor in the department of microbiology and immunology George Liechti, PhD, in the press release.
In a study to gauge the vaccine’s potential, researchers vaccinated mice and then exposed them to the mouse pathogen Chlamydia muridarum, which is related to the human Chlamydia trachomatis.
The mice “showed faster infection clearance, lower bacterial levels, and less tissue damage compared to traditional vaccines,” the press release states.
This new understanding of how antioxidants work is opening avenues of research that could lead to vaccines for radiation exposure and treatments for radiation illnesses. Clinical laboratories will play a role in screening patients and helping pathologists determine the most effective treatments.
—Stephen Beale
Related Information:
How ‘Conan the Bacterium’ Withstands Extreme Radiation
‘Conan the Bacterium’ Can Survive Extreme Radiation, and Scientists Finally Know Why
Radiation-Resistant ‘Extremophile’ Microbe Dubbed ‘Conan the Bacterium’ Inspires New Antioxidant
USU Researchers Develop New Vaccine Candidate to Combat Chlamydia