Abstract:
Abstract: Bacteria that associate with living hosts require intricate mechanisms to detect and
respond to host defenses. Part of the early host defense against invading bacteria is the production
of reactive oxygen species, and xanthine oxidase is one of the main producers of such agents. The
end-product of the enzymatic activity of xanthine oxidase, urate, was previously shown to be the
natural ligand for Deinococcus radiodurans-encoded HucR and it was shown to attenuate DNA
binding by Agrobacterium tumefaciens-encoded PecS and Burkholderia thailandensis-encoded
MftR, all members of the multiple antibiotic resistance regulator (MarR) family. We here show that
residues involved in binding urate and eliciting the DNA binding antagonism are conserved in a
specific subset of MarR homologs. Although HucR controls endogenous urate levels by regulating a
uricase gene, almost all other homologs are predicted to respond to exogenous urate levels and to
regulate a transmembrane transport protein belonging to either the drug metabolite transporter
(DMT) or the major facilitator superfamily (MFS), as further evidenced by the presence of conserved
binding sites for the cognate transcription factor within the respective promoter regions. These data
suggest the use of orthologous genes for different regulatory purposes. We propose the designation
UrtR (urate responsive transcriptional regulator) for this distinct subfamily of MarR homologs based
on their common mechanism of urate-mediated attenuation of DNA binding.
