Deinococcus radiodurans can withstand radiation doses thousands of times higher than what would kill a human. Credit: USU/Michael Daly

Deinococcus radiodurans is a bacterium that can withstand radiation doses thousands of times higher than what would kill every other living organism, including humans.

The secret behind the bacteria's ability to tolerate the harshest of conditions is the presence of a collection of simple metabolites, which combine with manganese to form a powerful antioxidant. Now, for the first time, chemists at Northwestern University and the Uniformed Services University (USU) have discovered exactly how this antioxidant works.

The discovery could eventually lead to new synthetic antioxidants for specific applications, such as protecting astronauts from intense cosmic radiation during deep-space missions, preparing for radiation emergencies and producing radiation-inactivated vaccines.

In the new study published in PNAS, Northwestern's Brian Hoffman and USU's Michael Daly characterized a synthetic designer antioxidant named MDP, inspired by Deinococcus radiodurans' resilience. MDP's components -- manganese ions, phosphate and a small peptide -- form a ternary complex that is a much more powerful protectant from radiation damage than manganese combined with either of the other individual components alone.

"It is this ternary complex that is MDP's superb shield against the effects of radiation," said Hoffman, a professor of chemistry at Northwestern. "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. This study has provided the key to understanding why this combination is such a powerful and promising radioprotectant."

Building on their efforts to understand the microbe's radiation resistance, Hoffman and Daly 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.

This line of research is not new to Hoffman or Daly. In fact, the newest study published in PNAS builds off the duo's previous research during which they sought to better understand Deinococcus radiodurans' predicted ability to withstand radiation on Mars. In that study, Hoffman's team at Northwestern used an advanced spectroscopy technique to measure the accumulation of manganese antioxidants in the microbes' cells.

The team discovered that the size of the radiation dose a microorganism or its spores can survive directly correlates with the amount of manganese antioxidants it contains. In other words, more manganese antioxidants mean more resistance to intense radiation.

In even earlier studies, other researchers discovered Deinococcus radiodurans can survive 25,000 grays (or units of x- and gamma-rays). But, in their 2022 study, Hoffman and Daly found that the bacterium, when dried and frozen, could weather 140,000 grays of radiation -- a dose 28,000 times greater than what would kill a human.

Theoretically, that means any frozen microbes buried on Mars could survive the onslaught of galactic cosmic radiation and solar protons to this day. It also gives hope and a possible path forward for astronauts interested in lengthy deep-space missions.

Biomedically, in another of Daly's recent studies, his team used advanced paramagnetic resonance spectroscopy to determine that MDP is effective in the preparation of irradiated polyvalent vaccines. Irradiated vaccines are a popular research target since they can generate higher humoral immune responses and protect against a variety of different bacteria. They are also relatively inexpensive and quick to manufacture.

"This new understanding of MDP could lead to the development of even more potent manganese-based antioxidants for applications in health care, industry, defense and space exploration," concluded Daly.