Inhibition of SOS Response by Nitric Oxide Donors in Blocks Toxin Production and Hypermutation.

BACKGROUND

Previous reports have differed as to whether nitric oxide inhibits or stimulates the SOS response, a bacterial stress response that is often triggered by DNA damage. The SOS response is an important regulator of production of Shiga toxins (Stx) in Shiga-toxigenic (STEC). In addition, the SOS response is accompanied by hypermutation, which can lead to emergence of antibiotic resistance. We studied these effects as well as .

RESULTS

Nitric oxide donors inhibited induction of the SOS response by classical inducers such as mitomycin C, ciprofloxacin, and zidovudine, as measured by assays for RecA. Nitric oxide donors also inhibited Stx toxin protein production as well as RNA and . experiments were performed with ligated ileal segments in the rabbit using a 20 h infection. The NO donor S-nitroso-acetylpenicillamine (SNAP) reduced hypermutation and , as measured by emergence of rifampin resistance. SNAP blocked the ability of the RecA protein to bind to single-stranded DNA in an electrophoretic mobility shift assay (EMSA) , an early event in the SOS response. The inhibitory effects of SNAP were additive with those of zinc acetate.

CONCLUSIONS

Nitric oxide donors blocked the initiation step of the SOS response. Downstream effects of this blockade included inhibition of Stx production and of hypermutation. Infection of rabbit loops with STEC resulted in a downregulation, rather than stimulation, of nitric oxide host defenses at 20 h of infection.