Bacteria commonly synthesize superoxide dismutases (SOD) to eliminate superoxide anions (Lynch & Kuramitsu, 2000). Hydrogen peroxide is scavenged in most organisms by peroxidases and catalases (Chelikani et al., 2004; Imlay, 2008). Oxidative DNA damage is an important source of mutagenesis. It is known that the formation of 8-oxoG (or GO) can give rise to mutations in E. coli (Bridges, 1993; Bridges et al., 1996) and in other bacteria, for example, in pseudomonads (Saumaa et al., 2002, 2007; Mandsberg et al., 2009). In order to alleviate the mutagenic effect of 8-oxoG, bacteria have developed an oxidized guanine (GO) repair system (Michaels & Miller, 1992; Michaels

et al., 1992). Oxidatively damaged guanine is removed from DNA by MutM glycosylase, whereas MutY glycosylase removes adenine from A·(8-oxoG)

and A·G mispairings. MutT pyrophosphohydrolase hydrolyzes 8-oxodGTP find more to 8-oxodGMP and pyrophosphate to prevent its incorporation into DNA. Products of oxidative damage of adenine have also been shown to be mutagenic (Kamiya, 2003), but have received less attention. Additionally, several premutagenic oxidized pyrimidines such as thymine glycol, 5-hydroxycytosine, dihydrothymine this website and dihydrouracil are common lesions in DNA (Dalhus et al., 2009). The generation of ROS is important in pathogenesis. Oxidation of bacterial DNA by ROS presents an increased risk for the occurrence of hypermutable P. aeruginosa with mutations that confer adaptation of the bacteria in the lung of CF patients and persistence of the infection (Ciofu et al., 2005). The chronic infections by P. aeruginosa are associated with biofilm formation. Recent studies have identified a role of oxidative stress in generating mutation and phenotypic variation in P. aeruginosa biofilm (Allegrucci & Sauer,

2008; Boles & Singh, 2008; Mai-Prochnow et al., 2008). Although the oxygen tension is low within the biofilm structures, it has been reported that respiration can produce enough oxidative stress to produce DNA damage, and that some biofilm bacteria may express lower levels of antioxidant enzymes such as catalase and SOD, thereby increasing the mutation frequency (Hassett et al., 1999; Driffield et al., Tryptophan synthase 2008). The results of Boles & Singh (2008) suggest that the genetic variation in P. aeruginosa biofilm might be caused by the mutagenic repair of DNA double-strand breaks (DSBs) caused by oxidative stress. The involvement of ROS in the generation of mutations has also been studied in starving P. putida (Saumaa et al., 2002, 2007; Tarassova et al., 2009). Recently, we discovered that the frequency of emergence of base substitution mutants is significantly increased in long-term-starved populations of P. putida deficient in stationary-phase-specific sigma factor RpoS (Tarassova et al., 2009).