Nicknamed the ‘Conan bacteria’ for its extraordinary ability to tolerate the harshest conditions, Deinococcus radiodurans can withstand radiation doses thousands of times higher than what would kill a human (and any other organism). The secret to this impressive resistance is the presence of a series of simple metabolites that combine with manganese to form a powerful antioxidant. Now, chemists at Northwestern University and the Uniformed Services University (USU) have discovered how this antioxidant works. Their findings are published in a study in the journal ‘PNAS‘.
In this work, the researchers describe an artificial antioxidant, called MDP, inspired by the resilience of Deinococcus radiodurans. They found that the components of MDP (manganese ions, phosphate, and a small peptide) form a ternary complex that is a much more powerful protector against radiation damage than manganese combined with any of the other individual components alone.
This discovery could lead to the creation of new synthetic antioxidants designed specifically for human needs. Its applications include protecting astronauts against intense cosmic radiation during deep space missions, preparing for radioactive emergencies, or producing radiation-inactivated vaccines.
“We have known for a long time that manganese and phosphate ions together form a powerful antioxidant, but discovering and understanding the ‘magic’ power provided by the addition of the third component is a breakthrough,” explains Northwestern’s Brian Hoffman, who led the study with Michael Daly of USU. “This study has provided the key to understanding why this combination is such a powerful and promising radioprotectant.”
The incredible hulk of the microbial world
The new study builds on previous research from Hoffman and Daly’s collaboration, during which they sought to better understand the predicted ability of D. radiodurans to withstand radiation on Mars. In that research, Hoffman’s team at Northwestern used an advanced spectroscopy technique to measure the accumulation of manganese antioxidants in microbial cells.
According to Hoffman and Daly, the radiation dose that a microorganism or its spores can survive is directly correlated to the amount of manganese antioxidants it contains. In other words, more manganese antioxidants mean more resistance to intense radiation.
In previous studies, other researchers found that Conan can survive 25,000 grays (or units of x-rays and gamma rays). But, in their 2022 study, Hoffman and Daly found that the bacteria, when dried and frozen, can withstand 140,000 grays of radiation, a dose 28,000 times greater than what would kill a human. Therefore, if there are dormant, frozen microbes buried on Mars, they may have survived the onslaught of galactic cosmic radiation and solar protons to this day.
The power of three
Building on their efforts to understand the microbe’s radiation resistance, Hoffman and Daly’s team investigated a designer decapeptide called DP1. When combined with phosphate and manganese, DP1 forms the free radical scavenging agent MDP, which successfully protects cells and proteins against radiation damage. In another recent study, Daly and colleagues found that MDP is effective in preparing multivalent irradiated vaccines.
Using advanced paramagnetic resonance spectroscopy, the team revealed that the active ingredient in MDP is a ternary complex: a precise assembly of phosphate and peptide linked to manganese.
“This new understanding of MDP could lead to the development of even more potent manganese-based antioxidants for applications in healthcare, industry, defense and space exploration,” Daly said.
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