How Do Some Bacteria Survive Ionizing Radiation?

Amazing stuff! This is an article based on past research. This is a review article of a review article by one of the leading researchers in this field as it appears.

The secret sauce seems to be manganese. 

"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. ...

It was discovered ... at an agricultural research station in Oregon. In the 1950s, researchers at the station were experimenting with using ionizing radiation to sterilize canned food. 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. ...

“One of the key findings from that large body of work was the high dependence of these microorganisms on manganese,” ... 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. ...

“We were observing the emergent antioxidant’s chemistry: three components where they do much more together—much, much more together—than individually,” ...  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. ..."

From the abstract:

"The family Deinococcaceae exhibits exceptional radiation resistance and possesses all the necessary traits for surviving in radiation-exposed environments. Their survival strategy involves the coupling of metabolic and DNA repair functions, resulting in an extraordinarily efficient homologous repair of DNA double-strand breaks (DSBs) caused by radiation or desiccation. The keys to their survival lie in the hyperaccumulation of manganous (Mn2+)-metabolite antioxidants that protect their DNA repair proteins under extreme oxidative stress and the persistent structural linkage by Holliday junctions of their multiple genome copies per cell that facilitates DSB repair. 

This coupling of metabolic and DNA repair functions has made polyploid Deinococcus bacteria a useful tool in environmental biotechnology, radiobiology, aging, and planetary protection.

The review highlights the groundbreaking contributions of the late Robert G.E. Murray to the field of Deinococcus research and the emergent paradigm-shifting discoveries that revolutionized our understanding of radiation survivability and oxidative stress defense, demonstrating that the proteome, rather than the genome, is the primary target responsible for survivability. These discoveries have led to the commercial development of irradiated vaccines using Deinococcus Mn-peptide antioxidants and have significant implications for various fields."

How Do Some Bacteria Survive Ionizing Radiation? | The Scientist "Integrity of the proteome, rather than the genome, underlies the remarkable radioresistance of Deinococcus radiodurans."

The scientific revolution that unraveled the astonishing DNA repair capacity of the Deinococcaceae: 40 years on (open access)

Fig. 3. Sequential recombinational pathways for double-strand break (DSB) repair in Deinococcus radiodurans that benefit from persistent linkage by Holliday junctions.

Water bear genes provide protection from radiation damage

Amazing stuff!

"A newly described species of tardigrade (Hypsibius henanensis) is giving scientists insights into what makes these tiny eight-legged creatures so resistant to radiation. Scientists sequenced the genome of this new species and identified thousands of genes that become more active when exposed to radiation. These processes point to a sophisticated defence system that involves protecting DNA from the damage that radiation causes and repairing any breaks that do occur. They hope that these insights could be harnessed to protect humans exposed to radiation during space missions or to improve cancer treatment."

"... One of the genes, called TRID1, encodes a protein that helps to repair double-strand breaks in DNA by recruiting specialized proteins at sites of damage. “...

The researchers also estimate that 0.5–3.1% of the tardigrade’s genes were acquired from other organisms through a process known as horizontal gene transfer. A gene called DODA1, which seems to have been acquired from bacteria, enables tardigrades to produce four types of antioxidant pigments called betalains. These pigments can mop up some of the harmful reactive chemicals that radiation causes to form inside cells, which account for 60–70% of radiation’s damaging effects. ..."

From the editor's summary and abstract:

"Editor’s summary

Tardigrades are small invertebrates renowned for their resistance to harsh environmental conditions, including ionizing radiation that would kill many organisms. Li et al. now describe a previously unknown species of tardigrade, Hypsibius henanensis, and investigate how these organisms respond to radiation treatment using genome, transcriptome, and proteome analyses. The mechanisms include induction of biosynthesis of betalain pigments and up-regulation of both tardigrade-specific and more widely distributed pathways for stress response and DNA damage repair. ...

Abstract

INTRODUCTION

Tardigrades, commonly known as water bears, are small ecdysozoans renowned for their tolerance to extreme environments, including ultrahigh radiation. They exhibit exceptional resistance to ionizing radiation, withstanding doses as high as 3000 to 5000 grays (Gy) of gamma rays, which is ∼1000 times the lethal dose for humans. The mechanism of radiotolerance in tardigrades remains largely unclear.

RATIONALE

A multi-omics data mining strategy holds immense potential for unraveling the mechanisms of extreme environmental tolerance in tardigrades. By integrating genomics, transcriptomics, and proteomics, we decipher the genome-wide landscape of antiradiation response. After differential analysis and screening of key molecules, we used biochemical and cellular methodologies to validate their functional roles and delve into the underlying molecular mechanisms.

RESULTS

We obtained a well-annotated chromosome-level genome of a radiotolerant species, Hypsibius henanensis sp. nov., newly identified in this study. Through differential analysis of transcriptome and proteome after heavy ion radiation, we identified 2801 differentially expressed genes (DEGs). On the basis of evolutionary and functional analyses of these DEGs, we characterized the radiotolerance mechanisms from three different perspectives:
First, horizontal gene transfer (HGT) may be an important evolutionary event that substantially contributes to the development of tardigrades’ ultrahigh radiation resistance. We identified a DOPA (dihydroxyphenylalanine) dioxygenase gene, DODA1, that we propose is a product of HGT from bacteria to tardigrades. DODA1 is responsive to radiation and confers radiation resistance through biosynthesis of betalains, a kind of pigment that exists mainly in plants, a few fungi, and bacteria. Next, we found that a tardigrade-specific radiation-induced disordered protein, TRID1, accelerates DNA damage repair by means of a process that encompasses phase separation.
Lastly, non-tardigrade-specific genes also contribute to the tardigrades’ radiotolerance. We found that two mitochondrial respiratory chain complex assembly proteins, BCS1 [ubiquinol–cytochrome c reductase (bc1) synthesis] and NDUFB8 [NADH dehydrogenase (ubiquinone) 1 beta subcomplex subunit 8], are pronouncedly up-regulated and then accumulate to accelerate NAD+ (nicotinamide adenine dinucleotide) regeneration for poly(adenosine diphosphate–ribosyl)ation (PARylation) and subsequent PARP1 [poly(adenosine diphosphate–ribose) polymerase 1]–mediated DNA damage repair.

CONCLUSION

Through multi-omics data mining and functional validation, our work uncovers a role for DODA1 in activation of an amino acid metabolism pathway (tyrosine-DOPA-betalains axis) for reactive oxygen species mitigation, elucidates tardigrade-specific TRID1-mediated phase separation in contributing to radiotolerance by enhancing double-strand break repair efficiency, and provides insight into the participation of BCS1 and NDUFB8 in acceleration of mitochondrial oxidative phosphorylation and NAD+ regeneration. Functional research on these radiotolerance mechanisms of tardigrades will broaden our understanding of cell survival under extreme conditions."

Nature Briefing: Cancer

New species of tardigrade reveals secrets of radiation-resisting powers "Knowing the genes responsible for water bears’ radiation tolerance could lead to diverse applications, from cancer treatment to space exploration."

Multi-omics landscape and molecular basis of radiation tolerance in a tardigrade (no public access)

Schematic of mechanisms that confer radiotolerance to H. henanensis sp. nov.

Low-dose ionising radiation linked to higher cancer risk among nuclear workers and medical imaging staff than previously thought

How much significantly higher is the risk? One study does not make a risk. The study does not seem to mention the effect on patients.

To choose the survivors of the atomic bombs on Japan as the "primary basis" for this study seems dubious. This is an extreme choice for a basis.

What would be the consequences? Fewer medical imaging studies? Are there too many such studies?

"Long-term exposure to low-dose radiation is linked to an increased risk of cancer, according to a study led by the University of California, Irvine. In the U.S., radiation exposure for the average person doubled between 1985 and 2006, mainly from medical imaging procedures such as CT scans, highlighting the need for its judicious use."

"... No patients were involved in setting the research question, the outcome measures, or the design and implementation of the study. ...
The study of Japanese survivors of the atomic bombs serves as the primary basis for the quantitative risk estimates used in radiation protection. ..."

From the abstract:

"Abstract

Objective To evaluate the effect of protracted low dose, low dose rate exposure to ionising radiation on the risk of cancer.

Design Multinational cohort study.

Setting Cohorts of workers in the nuclear industry in France, the UK, and the US included in a major update to the International Nuclear Workers Study (INWORKS).

Participants
309 932 workers with individual monitoring data for external exposure to ionising radiation and a total follow-up of 10.7 million person years.

Main outcome measures
Estimates of excess relative rate per gray (Gy) of radiation dose for mortality from cancer.

Results
The study included 103 553 deaths, of which 28 089 were due to solid cancers. The estimated rate of mortality due to solid cancer increased with cumulative dose by 52% (90% confidence interval 27% to 77%) per Gy, lagged by 10 years. Restricting the analysis to the low cumulative dose range (0-100 mGy) approximately doubled the estimate of association (and increased the width of its confidence interval), as did restricting the analysis to workers hired in the more recent years of operations when estimates of occupational external penetrating radiation dose were recorded more accurately. Exclusion of deaths from lung cancer and pleural cancer had a modest effect on the estimated magnitude of association, providing indirect evidence that the association was not substantially confounded by smoking or occupational exposure to asbestos.

Conclusions
This major update to INWORKS provides a direct estimate of the association between protracted low dose exposure to ionising radiation and solid cancer mortality based on some of the world’s most informative cohorts of radiation workers. The summary estimate of excess relative rate solid cancer mortality per Gy is larger than estimates currently informing radiation protection, and some evidence suggests a steeper slope for the dose-response association in the low dose range than over the full dose range. These results can help to strengthen radiation protection, especially for low dose exposures that are of primary interest in contemporary medical, occupational, and environmental settings."

Low-dose ionising radiation linked to higher cancer risk than previously thought | Research | Chemistry World Multi-decade study reveals greater rates of fatal solid cancers among nuclear workers than previously estimated

UC Irvine-led study links low-dose radiation to higher cancer risk Caution warranted given increased public exposure in recent decades

Cancer mortality after low dose exposure to ionising radiation in workers in France, the United Kingdom, and the United States (INWORKS): cohort study

What is wrong with the chart below? Use of linear regression, while nonlinear is strongly suggested by the data. One may also notice the the confidence intervals are spreading enormously beyond 250 mGy.

Fig 1 Relative rate of mortality due to solid cancer by categories of cumulative colon dose, lagged 10 years in INWORKS. Bars indicate 90% confidence intervals, and purple line depicts fitted linear model for change in excess relative rate of solid cancer mortality with dose. Strata: country, age, sex, birth cohort, socioeconomic status, duration employed, neutron monitoring status