, 1998; Smith et al., 2002; Aertsen et al., 2004; Liveris et al., 2004) that, when bound to RecA, induces its co-proteinase activity, which enhances autocatalysis of the LexA repressor and activates the SOS response. This results in a choreographed transcription

of multiple genes (UvrA, UvrB, UvrC, UvrD, DNA polymerase I, DNA ligase), which repair intrachain DNA damage by nucleotide excision (Black et Selleckchem Vorinostat al., 1998; Aertsen et al., 2004; Fry et al., 2005; Maul & Sutton, 2005). Not all bacteria have an SOS response or induction of uvrA transcription in response to DNA damage. In Pseudomonas aeruginosa (Rivera et al., 1997) and Neisseria spp. (Black et al., 1998; Davidsen et al., 2007), DNA damage does not trigger an SOS response and does not induce uvrA, suggesting that E. coli and B. subtilis paradigms regarding the regulation of uvrA are not universal. Because many host defenses involve production of DNA-damaging reactive oxygen species (ROS) and reactive nitrogen species (RNS), the ability of pathogenic bacteria to repair damaged DNA is important to their survival in hosts. In Mycobacterium tuberculosis, uvrA mutants show decreased ability to survive within macrophages (Graham & Clark-Curtiss, 1999) and uvrB mutants are attenuated in mice (Darwin & Nathan, 2005). Similarly, in Helicobacter

pylori and Yersinia sp., defects in uvrA are accompanied Sirolimus price by attenuation in mice (Bijlsma et al., 2000; Garbom et al., 2004). These experimental results strongly suggest that lack of DNA repair

mediated by the uvrA gene product attenuates bacterial pathogens because they cannot overcome the DNA-damaging systems of the host (Janssen et al., 2003). The genome of Borrelia burgdorferi, the cause of Lyme disease, contains a minimal set of genes devoted to DNA repair and appears to lack an SOS response despite the presence of orthologues Neratinib manufacturer of uvrA, uvrB, uvrD, DNA polymerase I and DNA ligase (Fraser et al., 1997). It also lacks an orthologue for the repressor of the SOS response, lexA, and none of the genes potentially involved in DNA repair display consensus LexA binding boxes similar to those found in E. coli (Fraser et al., 1997). recA also does not appear to be involved in repair of UV-induced DNA damage in B. burgdorferi (Liveris et al., 2004; Putteet-Driver et al., 2004). Borrelia burgdorferi is exposed to antibacterial levels of ROS and RNS in infected ticks (Pereira et al., 2001) and mammals (Benach et al., 1984; Cinco et al., 1997; Hellwage et al., 2001) intracellularly, following phagocytosis, and extracellularly, by diffusion from intracellular sources or by production at the phagocyte plasma membrane (Putteet-Driver et al., 2004). Borrelia burgdorferi can also be exposed to solar UVB radiation in the erythema migrans skin lesion (Born & Born, 1987).