An Antioxidant from a Radioresistant Bacterium: its role in Radiation Resistance beyond Oxidative Stress Tolerance

In living cells, reactive oxygen/nitrogen species (ROS/RNS) are produced as the byproducts of metabolic processes during aerobic respiration or during growth under unfavorable conditions. Organisms have evolved different strategies, involving both antioxidant enzymes and non-enzymatic antioxidant molecules to detoxify these species. These reactive molecules, if not detoxified, can cause oxidative damage to cellular components, resulting in metabolic defects, ageing, mutagenesis and eventually cell death. The level of oxidative stress tolerance, therefore, depends on the ability of an organism to counteract the deleterious effects of these reactive species. Organisms having higher tolerance to oxidative stress are believed to effectively scavenge ROS and hence, are good model systems to study oxidative stress tolerance mechanisms. These organisms can also be a preferred source for identification of novel antioxidant molecules. Deinococcus radiodurans has been widely characterized for its exceptionally high tolerance to γ radiation and hydrogen peroxide. The γ radiation produces both DNA single strand and double strand breaks (DSB) and imposes oxidative stress by generating reactive oxygen species. We are, currently, involved in understanding the molecular mechanisms underlying the extraordinary tolerance of Deinococcus radiodurans to ionizing radiation by studying the DNA repair as well as the oxidative stress tolerance in Deinococcus radiodurans. Deinococcus genome encodes a genetic system for the synthesis of pyrroloquinoline–quinone (PQQ) with anticipated antioxidant properties. We characterized PQQ for its antioxidant properties both in vivo and in vitro. Escherichia coli, a radiation and oxidative stress sensitive bacterium, when genetically engineered for making PQQ, showed higher tolerance to both oxidative stress and UVC radiation. On the other hand, the Deinococcus cells lacking PQQ become hypersensitive to γ radiation, perhaps, due to a defect in both oxidative stress tolerance and DSB repair. The proteins through which PQQ supports DNA repair and radiation tolerance were characterized from both E. coli and Deinococcus. PQQ stimulates the activity of these proteins in vitro. Deletion of a gene encoding deinococcal protein having PQQ binding site from this bacterial genome makes it sensitive to g radiation. These findings together suggest an additional role of PQQ in extraordinary radiation resistance and DSB repair in this bacterium. Further studies will be required to understand the mechanism of PQQ action in radiation resistance and DSB repair in bacteria and other organisms.