ArgR of Streptomyces coelicolor Is a Pleiotropic Transcriptional Regulator: Effect on the Transcriptome, Antibiotic Production, and Differentiation in Liquid Cultures.

Angel Manteca,Paula Yagüe,Rubén Álvarez-Álvarez,Paloma Liras,Rosario Pérez-Redondo,Alma Botas,Antonio Rodríguez-García

doi:10.3389/fmicb.2018.00361

Abstract

ArgR is a well-characterized transcriptional repressor controlling the expression of arginine and pyrimidine biosynthetic genes in bacteria. In this work, the biological role of Streptomyces coelicolor ArgR was analyzed by comparing the transcriptomes of S. coelicolor ΔargR and its parental strain, S. coelicolor M145, at five different times over a 66-h period. The effect of S. coelicolor ArgR was more widespread than that of the orthologous protein of Escherichia coli, affecting the expression of 1544 genes along the microarray time series. This S. coelicolor regulator repressed the expression of arginine and pyrimidine biosynthetic genes, but it also modulated the expression of genes not previously described to be regulated by ArgR: genes involved in nitrogen metabolism and nitrate utilization; the act, red, and cpk genes for antibiotic production; genes for the synthesis of the osmotic stress protector ectoine; genes related to hydrophobic cover formation and sporulation (chaplins, rodlins, ramR, and whi genes); all the cwg genes encoding proteins for glycan cell wall biosynthesis; and genes involved in gas vesicle formation. Many of these genes contain ARG boxes for ArgR binding. ArgR binding to seven new ARG boxes, located upstream or near the ectA-ectB, afsS, afsR, glnR, and redH genes, was tested by DNA band-shift assays. These data and those of previously assayed fragments permitted the construction of an improved model of the ArgR binding site. Interestingly, the overexpression of sporulation genes observed in the ΔargR mutant in our culture conditions correlated with a sporulation-like process, an uncommon phenotype.

Highlights

Biosynthesis of amino acids is regulated in microorganisms when these nutrients are abundant in the culture medium
Construction of a New Model to Analyse ArgR Binding in S. coelicolor
Most evident ArgR binding sites were identified in the arginine biosynthesis promoters of S. clavuligerus (Rodríguez-García et al, 1997) and S. coelicolor (Pérez-Redondo et al, 2012)

Summary

Introduction

Biosynthesis of amino acids is regulated in microorganisms when these nutrients are abundant in the culture medium. The ArgR protein is widely distributed in bacteria, acting mostly as a repressor of genes for arginine uptake and biosynthesis (Cunin et al, 1983) but may act as an activator, as in the aot operon for arginine and ornithine uptake in Pseudomonas (Nishijyo et al, 1998; Lu et al, 2004). It is an essential accessory protein in the site-specific resolution of ColE1 oligomers in E. coli (Stirling et al, 1988). The Bacillus AhrC repressor, homologous to ArgR, represses the argCAEBD-cpaargF gene cluster in the presence of arginine (Smith et al, 1989) and activates arginine catabolism genes in cooperation with the RocR activator (Gardan et al, 1997)

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Conclusion