Protein Oxidation Implicated as the Primary Determinant of Bacterial Radioresistance

Abstract

In the hierarchy of cellular targets damaged by ionizing radiation (IR), classical models of radiation toxicity place DNA at the top. Yet, many prokaryotes are killed by doses of IR that cause little DNA damage. Here we have probed the nature of Mn-facilitated IR resistance in Deinococcus radiodurans, which together with other extremely IR-resistant bacteria have high intracellular Mn/Fe concentration ratios compared to IR-sensitive bacteria. For in vitro and in vivo irradiation, we demonstrate a mechanistic link between Mn(II) ions and protection of proteins from oxidative modifications that introduce carbonyl groups. Conditions that inhibited Mn accumulation or Mn redox cycling rendered D. radiodurans radiation sensitive and highly susceptible to protein oxidation. X-ray fluorescence microprobe analysis showed that Mn is globally distributed in D. radiodurans, but Fe is sequestered in a region between dividing cells. For a group of phylogenetically diverse IR-resistant and IR-sensitive wild-type bacteria, our findings support the idea that the degree of resistance is determined by the level of oxidative protein damage caused during irradiation. We present the case that protein, rather than DNA, is the principal target of the biological action of IR in sensitive bacteria, and extreme resistance in Mn-accumulating bacteria is based on protein protection.

Element analysis of the eutardigrades Richtersius coronifer and Milnesium cf. asiaticum using Particle Induced X-ray Emission (PIXE)

“…Our analysis did not provide any support for the manganese hypothesis proposed by Daly et al (2004Daly et al ( , 2007, a hypothesis which suggests that manganese plays a role in tolerance to desiccation and radiation by preventing the action of damaging reactive oxygen species. The two tardigrade species investigated had very low levels of manganese, and the element was only found in a minority of specimens.…”

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Plasmas meet nanoparticles—where synergies can advance the frontier of medicine

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