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.
Highlights
The amount of DNA damage caused by a given dose of cradiation for resistant and sensitive bacteria is very similar [1,2]
The emphasis has shifted to understanding why bacteria such as Deinococcus radiodurans are extremely resistant to ionizing radiation (IR), by focusing on DNA repair systems expressed during recovery from high doses of IR
Recent studies have shown that extreme levels of bacterial IR resistance correlate with high intracellular Mn(II) concentrations, and resistant and sensitive bacteria are susceptible to IR-induced DNA damage
Summary
The amount of DNA damage caused by a given dose of cradiation for resistant and sensitive bacteria is very similar [1,2]. We have reported a relationship between intracellular Mn/Fe concentration ratios and bacterial survival following exposure to IR, in which the most-resistant cells contained about 300 times more Mn and about three times less Fe than the most-sensitive cells [1]. Restricting Mn(II) during growth of D. radiodurans significantly lowered the Mn content of wild-type cells, and IR resistance to levels quantitatively similar to several highly sensitive D. radiodurans DNA repair mutants [1]. The nature of Mnfacilitated IR resistance was undefined, and the question of why many bacteria that encode a complement of repair functions are killed by doses of IR that cause little DNA damage has not been resolved [1,4,5]
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