Newswise — BETHESDA, Md. – New insight into the structural nature of Deinococcus manganese complexes in the world’s toughest microbe, Deinococcus radiodurans, gained by using advanced spectroscopy techniques, may ultimately accelerate the development of pharmaceuticals aimed at slowing down the aging process, prevent some severe side effects of radiation therapy and chemotherapy, reduce the chances of skin cancer following exposure to UV rays from the sun, and in the preparation of irradiated vaccines, according to a breakthrough study, “Responses of Mn2+ Speciation in Deinococcus radiodurans and Escherichia coli to Gamma-Radiation by Advanced Paramagnetic Resonance Methods,” published in the March 25 edition of the Proceedings of the National Academy of Sciences USA.
The collaborative study was led by Michael J. Daly, Ph.D., professor at the Uniformed Services University of the Health Sciences (USU), Department of Pathology, and Brian Hoffman, Ph.D., professor at Northwestern University, Department of Chemistry, and reveals the structure of manganese-based chemical antioxidants in Deinococcus radiodurans. The bacterium can survive massive exposures to gamma-radiation, ultraviolet radiation, and other agents which kill cells by generating dangerous oxygen radicals. The advanced spectroscopy techniques applied shed light on how Deinococcus Mn complexes defend cells from radiation, and how to better harness their potent antioxidant properties for practical purposes.
Daly’s team previously reported that D. radiodurans accomplishes its astonishing survival feats in an unexpected way – by shielding its enzymes from oxidative damage using a mechanism which involves divalent Mn ions (Mn2+). This form of protection spares its DNA repair enzymes from radiation damage and allows the cells to reassemble their broken genomes with extraordinary efficiency. The current study shows that most Mn2+ in D. radiodurans cells is partnered with small nitrogenous compounds and inorganic phosphate, which form complexes that are impressively radioprotective. Following exposure to gamma-radiation, great differences were observed in the responses of Mn2+ complexes in D. radiodurans and Mn2+ complexes in radiation-sensitive bacteria – information which was used to identify the building blocks and structure of Mn2+ complexes as they exist in living D. radiodurans cells. The work represents a blueprint for synthesizing Deinococcus Mn complexes in the laboratory, with the prospect of developing new pharmaceutical interventions to combat oxidative stress in diverse settings, including the preparation of irradiated vaccines, during radiotherapy, against ultraviolet rays during sunbathing, and aging.
The three-year project was a collaboration between Daly’s group at USU, and a team led by Dr. Brian Hoffman at Northwestern University, Evanston, Ill. Funding was by the Air Force Office of Scientific Research Grant FA9550-10-1-0118 and Defense Threat Reduction Agency Grant HT9404-12-1-0020 (to M.J.D.) and by the National Institutes of Health (NIH) Grant HL13531 (to B.M.H.). For more information on Deinococcus research see, http://www.usuhs.mil/pat/deinococcus/index_20.htm.
USU is located on the grounds of the Naval Support Activity in Bethesda, Md., adjacent to the Walter Reed National Military Medical Center. The university provides military and public health-relevant education, research, service and consultation to the nation and the world, pursuing excellence and innovation during times of peace and war. For more information, visit www.usuhs.edu.
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Proceedings of the National Academy of Sciences (March 25, 2013)