Proteomic profiling of Deinococcus radiodurans with response to thioredoxin reductase inhibitor and ionizing radiation treatment

Abstract

This study explains the importance of cellular redox system in preserving the proteome of the radioresistant Deinococcus radiodurans. The thioredoxin reductase (TrxR) redox system was inhibited by ebselen (10 μM), and then the bacterium was exposed to 4 kGy of ionizing radiation. The differentially expressed proteins were analyzed using label-free quantitative (LFQ) proteomics. The 4 kGy radiation treatment increases the expression of stress response proteins like osmotically inducible protein OsmC, catalase, and metallophosphoesterase compared to control. Ebselen plus radiation treatment augments oxidoreductases proteins in D. radiodurans. Further, the proteins involved in glycolysis, tricarboxylic acetic acid (TCA) and proteins like proteases, peptidase, and peptide transporters were significantly decreased in the ebselen plus radiation group compared to radiation treated group. Further, ebselen plus radiation treatment increases the ATP-binding cassette (ABC) transporters involved in the efflux of toxic chemicals and nutrient uptake and the stress response related membrane protein like S-layer homology domain-containing protein in D. radiodurans. Thus, the results show that the altered redox status via inhibition of TrxR redox system significantly affects the expression of essential cellular proteins for the survival. The cellular content of D. radiodurans may be used to handle redox imbalances in the normal cells during cancer radiotherapy. Significance: Deinococcus radiodurans is a popular radioresistance organism with efficient antioxidant systems and DNA repair mechanisms. There are many antioxidant systems and small molecules that responsible for its resistance. The importance of thiol based antioxidant systems in its resistance property has not fully studied yet. Thioredoxin reductase is an important disulfide containing protein that involved in maintaining redox homeostasis. The TrxR inhibition affects the cell survival and synthesis of molecules against ionizing radiation. In this study we are reporting the effects of TrxR inhibitor on proteome of D. radiodurans upon ionizing radiation. This study reveals the significance of TrxR antioxidant system on the proteome of D. radiodurans. The inhibition of TrxR antioxidant system and the subsequent disturbances in the proteome content makes the organism vulnerable to oxidative stress.