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| Fig. 1: Direct and indirect DNA damage by ionizing radiation. (Source: Wikimedia Commons) |
Extremophiles are organisms that can survive and sometimes even thrive in environments that are considered hostile to other life forms. Most extremophiles are microorganisms like fungi and bacteria but there are other multicellular creatures that can be classified this way (tardigrades and insects). The ability of these organisms to withstand conditions such as extreme heat, cold, acidity, or salinity is a topic of much scrutiny since understanding these mechanisms has broad implications. Radiation resistance mechanisms are particularly appealing for their applications in medicine, hazardous waste management, and investigations concerning the parameters that limit life here and beyond earth. A number of studies have explored microbial adaptations to radiation exposure and here strategies employed in fungus such as changes in DNA repair functions, gene regulation, and proteome protection are briefly reviewed.
Exposure to ionizing radiation can have profound effects on the cellular components of all living organisms. Consequences of exposure can have lethal results whether by direct energy deposition of ionizing radiation or by the indirect interaction of reactive oxygen species (ROS). [1] (See Fig. 1.) Direct exposure occurs when radiation is incident unto DNA and damages the ability of cells to reproduce by interfering with chromosome replication or by altering DNA molecules. Indirect exposure occurs when radiation encounters other parts of the cell leading to the radiolytic decomposition of water. This is a major portion of damage as cells consist primarily of water molecules which may be fragmented into hydroxyl radicals (OH) and superoxide anions. These ROS can recombine with other fragments and ions to induce oxidative stress through the formation of an abundance of substances that are toxic to cells, like hydrogen peroxide.
Cryptococcus neoformans is a basidiomycetous yeast that can withstand high levels of ionizing radiation. A study by Kelley et al. assessed the viability of this fungus following an hour of exposure to gamma radiation emitted via a Cobalt-60 source between 50 and 300 Gy doses. [2] The number of viable colonogenic cells, or colony-forming units (CFUs), counted two days after exposure were found to be significant albeit diminishing with increased doses. This study highlighted C. neoformans resilience in oxidative conditions as well reporting significant viability following exposure to concentrations of up to 50 mM of H2O2 which greatly exceeds tolerance by the other yeasts and mammalian cells considered. In response to oxidative conditions the fungus upregulates genes related to antioxidant production, ROS-management, and DNA repairbut evidence of tRNA modification was not supported. [2] tRNA is a small molecule which plays a key role in protein synthesis. As this result contrasts with the oxidative response found in other microorganisms, the authors speculate that the evolutionary history of this species which predates other fungi by over 100 million years may have necessitated a tolerance for highly oxygenated conditions thus requiring constant ROS management.
The radiation resistance mechanism in fungus was also investigated from the aspect of melanin production by Dadachova et al. Compared to non-melanized cells, increased growth as indicated by higher CFUs and more dry weight biomass was observed in melanized cells for a number of species following radiation exposure. Melanized C. neoformans additionally exhibited enhanced electron transfer properties when exposure time to 14 Gy/min from a Cs-137 source was extended indicating enhanced metabolic activity. [3] This team speculates that the electronic complexity of melanin might allow them to efficiently scatter/trap photons and electrons, creating an effective radioprotective barrier that keeps free radicals from entering a cell and in turn prevents subsequent DNA damage. [4]
While the exact mechanistic principles behind melanin and genetic indicators for IR resistance are still not completely understood, there is recent evidence that a proteome protection strategy is a great predictor. Sharma et al. found that low molecular weight cell extracts of IR-resistant, Mn-accumulating bacteria specifically protect proteins from severe oxidative damage. This supports the hypothesis that proteins are the critical targets in IR sensitive cells. They also found a significant correlation between a simple measure of cellular Mn2+ speciation and their DSBD10 index. DSBD10 quantifies the efficiency of DSB (double strand break) repairs during exposure and the correlation is strong across the cell types that were investigated despite vast differences in the taxonomic status, genome size, and radio resistance. [5] Observing in species from archaea to bacteria and eukaryotes (including fungi and animals) this mechanism to withstand radiation far beyond what would be encountered in any natural environment, the authors posit that the accumulation of this antioxidant complex may have evolved in response to other oxidative perils rather than IR.
The studies reviewed here only hint at possible explanations for the mechanisms responsible for radiation resistance. While these findings elucidate the properties that enable the fungus kingdom to be among the most resilient order, the area remains mysterious and fascinating.
© Jillian Anderson. The author warrants that the work is the author's own and that Stanford University provided no input other than typesetting and referencing guidelines. The author grants permission to copy, distribute and display this work in unaltered form, with attribution to the author, for noncommercial purposes only. All other rights, including commercial rights, are reserved to the author.
[1] "Biological Effects of Radiation," U.S. Nuclear Regulatory Commission, March 2017.
[2] M. Kelley et al., "Ionizing Radiation and Chemical Oxidant Exposure Impacts on Cryptococcus neoformans Transfer RNAs," PLoS ONE 17, e0266239 (2022).
[3] D. Dadachova and A. Casadevall, "Ionizing Radiation: How Fungi Cope, Adapt, and Exploit With the Help of Melanin," Curr. Opin. Microbiol. 11, 525 (2008).
[4] E. Dadachova et al., "Ionizing Radiation Changes the Electronic Properties of Melanin and Enhances the Growth of Melanized Fungi," PLoS One 2, e457 (2007).
[5] A. Sharma et al.,"Across the Tree of life, Radiation Resistance Is Governed By Antioxidant Mn2+, Gauged by Paramagnetic Resonance," Proc. Natl. Acad. Sci. (USA) 114, E9253 (2017).
