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Abstract The genusVibrioincludes serious human pathogens, and mollusks are a significant reservoir for species such asV.vulnificus.Vibriospecies encode PecS, a member of the multiple antibiotic resistance regulator (MarR) family of transcription factors;pecSis divergently oriented topecM, which encodes an efflux pump. We report here thatVibriospecies feature frequent duplications ofpecS-pecMgenes, suggesting evolutionary pressures to respond to distinct environmental situations. The singleV.vulnificusPecS binds two sites within thepecS-pecMintergenic region with K_d = 0.3 ± 0.1 nM, a binding that is attenuated by the ligands xanthine and urate, except when promoter DNA is saturated with PecS. A unique target is found in the intergenic region between genes encoding the nitric oxide sensing transcription factor, NsrR, andnod; thenod-encoded nitric oxide dioxygenase is important for preventing nitric oxide stress. Reporter gene assays show that PecS-mediated repression of gene expression can be relieved in presence of ligand. Since xanthine and urate are produced as part of the oxidative burst during host defenses and under molluscan hypoxia, we propose that these intermediates in the host purine degradation pathway function to promote bacterial survival during hypoxia and oxidative stress.