How Do Some Bacteria Survive Ionizing Radiation?

For a human, experiencing a mere five grays (Gy) of ionizing radiation for just a few minutes can be lethal. But the bacterium Deinococcus radiodurans is made of tougher stuff. In liquid culture conditions, it can survive an acute blast of up to 25,000Gy and under chronic gamma radiation exposure (60Gy per hour), it not only survives, but thrives, continuing to grow and multiply.¹

The story of D. radiodurans began in a surprisingly pedestrian setting: It was discovered not at a nuclear test site or uranium mine, but at an agricultural research station in Oregon. In the 1950s, researchers at the station were experimenting with using ionizing radiation to sterilize canned food.² To their dismay, some of their heavily-irradiated corned beef still contained living microbes—they cultured the microbes and discovered D. radiodurans.

Over the following decades, scientists tried to identify the mechanisms underlying the microbe’s extreme radiation resistance. They found that the microbe could repair many more double-strand breaks within its DNA than other organisms. However, when its genome was sequenced in the early 2000s, the genes coding for DNA repair enzymes were surprisingly similar to other bacterial species, indicating that specialized repair enzymes probably weren’t responsible for the microbe’s remarkable hardiness.

D. radiodurans researchers, including Michael Daly, a radiation biologist at the Uniformed Services University, looked beyond the genome for answers. “One of the key findings from that large body of work was the high dependence of these microorganisms on manganese,” he said. Manganese can function as powerful antioxidant, which could help protect intracellular molecules from the reactive oxygen species (ROS) generated when ionizing radiation, such as gamma rays, interacts with water molecules in the cell. But there was more to the story than just manganese.

“After about a year of looking into what Deinococcus has in its cells, we came up with a recipe,” said Daly. “We were observing the emergent antioxidant’s chemistry: three components where they do much more together—much, much more together—than individually,” said Daly. In test tubes, mixing these three components—manganese, orthophosphate, and small peptides approximately 10–20 amino acids long—preserved the function of proteins and increased the survival of human cells in the face of high-dose radiation.³

Next, Daly teamed up with Brian Hoffman, an expert in metalloenzymes at Northwestern University, to investigate the properties of this three-part protector. They discovered that these three components bound together to create a stable ternary complex.⁴ While the combinations of manganese and orthophosphate or manganese and small peptides offered some protection from radiation, the ternary complex preserved the function of a DNA repair enzyme even when it was subjected to 60,000Gy.

This protection, said Hoffman, is likely due to the complex’s redox properties—it’s ability to accept or donate electrons. The complex catalyzes the conversion of highly damaging, negatively charged superoxide into the neutral hydrogen peroxide, which can cross the membrane and exit the cell.

Ionizing radiation produces different types of ROS; superoxide is particularly damaging to proteins, while other ROS are more damaging to DNA. Thus, said Hoffman, the ternary complex “doesn't protect the DNA from being broken, but it does protect the enzymes that repair the breaks. In other words, it's not good to get a flat tire, but if you have a patch for it, you're back in business. So, it's not good to have breaks, but the breaks can be healed.”

In the short-term, Daly is using this complex to create new types of whole-cell vaccines.⁵ A bacterial or viral particle surface bears different antigens, which can stimulate a more robust immune response than a single-antigen vaccine. While gamma radiation is an effective way to inactivate the microbe (required for safety), it can also damage the surface proteins that are essential for provoking the immune response. Using the manganese-antioxidant complex that protects these proteins from high-dose radiation, researchers can create immunogenic but harmless whole-cell vaccines for tricky or emerging pathogens. In the long-term, researchers hope that this manganese-antioxidant complex can aid in the treatment of cancer by helping protect healthy tissues from radiation therapy. One day, it may even provide protection for astronauts venturing into deep space.