Molecular control of gene expression byBrucellaBaaR, an IclR-family repressor

AbstractTheBrucella abortusgeneral stress response sigma factor, σE1, directly and indirectly regulates the transcription of dozens of genes that influence stress survival and host infection. Characterizing the functions of σE1regulated genes therefore contributes to understanding ofB. abortusphysiology and infection biology. Transcription of the IclR family regulator, Bab2_0215, is indirectly activated by σE1but its function remains undefined. We present a structural and functional characterization of Bab2_0215, which we have namedBrucellaadipic acid activated regulator (BaaR). BaaR adopts a classic IclR-family fold and directly regulates the transcription of two operons with predicted roles in carboxylic acid oxidation. BaaR binds two sites on chromosome II between baaR and a divergently transcribed hydratase/dehydrogenase (acaD2), and represses transcription. We identified three carboxylic acids (adipic acid tetradecanedioic acid, ε-aminocaproic acid) and a lactone (ε-caprolactone) that enhance transcription from thebaaRandacaD2promoters. However, neither the activating acids nor caprolactone enhance transcription by binding directly to BaaR. Induction ofbaaRtranscription by adipic acid requires the genebab2_0213, which encodes a major facilitator superfamily transporter, suggesting that Bab2_0213 transports adipic acid across the inner membrane. We conclude that a set of structurally related organic molecules activate transcription of genes repressed by BaaR. Our study provides molecular-level understanding of a gene expression program regulated downstream of σE1.