Molecular control of gene expression by Brucella BaaR, an IclR-type transcriptional repressor

Abstract

The general stress response sigma factor σ^E1 directly and indirectly regulates the transcription of dozens of genes that influence stress survival and host infection in the zoonotic pathogen Brucella abortus Characterizing the functions of σ^E1-regulated genes therefore would contribute to our understanding of B. abortus physiology and infection biology. σ^E1 indirectly activates transcription of the IclR family regulator Bab2_0215, but the function of this regulator remains undefined. Here, we present a structural and functional characterization of Bab2_0215, which we have named B rucella adipic acid-activated regulator (BaaR). We found that BaaR adopts a classic IclR-family fold and directly represses 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 it represses transcription of both genes. We identified three carboxylic acids (adipic acid, tetradecanedioic acid, and ϵ-aminocaproic acid) and a lactone (ϵ-caprolactone) that enhance transcription from the baaR and acaD2 promoters. However, neither the activating acids nor caprolactone enhanced transcription by binding directly to BaaR. Induction of baaR transcription by adipic acid required the gene bab2_0213, which encodes a major facilitator superfamily transporter, suggesting that Bab2_0213 transports adipic acid across the inner membrane. We conclude that a suite of structurally related organic molecules activate transcription of genes repressed by BaaR. Our study provides molecular-level understanding of a gene expression program in B. abortus that is downstream of σ^E1.

Keywords: Brucella; IclR; adipic acid; aminocaproic acid; bacteria; caprolactone; fatty acid metabolism; gene regulation; metabolism; transcription factor.