OsdR ofStreptomyces coelicolorand the Dormancy Regulator DevR ofMycobacterium tuberculosisControl Overlapping Regulons.
Two-component regulatory systems allow bacteria to respond adequately to changes in their environment. In response to a given stimulus, a sensory kinase activates its cognate response regulator via reversible phosphorylation. The response regulator DevR activates a state of dormancy under hypoxia inMycobacterium tuberculosis, allowing this pathogen to escape the host defense system. Here, we show that OsdR (SCO0204) of the soil bacteriumStreptomyces coelicoloris a functional orthologue of DevR. OsdR, when activated by the sensory kinase OsdK (SCO0203), binds upstream of the DevR-controlled dormancy genesdevR,hspX, and Rv3134c ofM. tuberculosis.In silicoanalysis of theS. coelicolorgenome combined within vitroDNA binding studies identified many binding sites in the genomic region aroundosdRitself and upstream of stress-related genes. This binding correlated well with transcriptomic responses, with deregulation of developmental genes and genes related to stress and hypoxia in theosdRmutant. A peak inosdRtranscription in the wild-type strain at the onset of aerial growth correlated with major changes in global gene expression. Taken together, our data reveal the existence of a dormancy-related regulon in streptomycetes which plays an important role in the transcriptional control of stress- and development-related genes.IMPORTANCEDormancy is a state of growth cessation that allows bacteria to escape the host defense system and antibiotic challenge. Understanding the mechanisms that control dormancy is of key importance for the treatment of latent infections, such as those fromMycobacterium tuberculosis. In mycobacteria, dormancy is controlled by the response regulator DevR, which responds to conditions of hypoxia. Here, we show that OsdR ofStreptomyces coelicolorrecognizes the same regulatory element and controls a regulon that consists of genes involved in the control of stress and development. Only the core regulon in the direct vicinity ofdosRandosdRis conserved betweenM. tuberculosisandS. coelicolor, respectively. Thus, we show how the system has diverged from allowing escape from the host defense system by mycobacteria to the control of sporulation by complex multicellular streptomycetes. This provides novel insights into how bacterial growth and development are coordinated with the environmental conditions.
Molecular Biotechnology, Institute of Biology Leiden, Leiden University, Leiden, The Netherlands.
Mia
M
Urem
Molecular Biotechnology, Institute of Biology Leiden, Leiden University, Leiden, The Netherlands.
Teunke
T
van Rossum
Microbial Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
Giselda
G
Bucca
Molecular Genetics, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
Geri F
GF
Moolenaar
Microbial Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
Emma
E
Laing
Molecular Biotechnology, Institute of Biology Leiden, Leiden University, Leiden, The Netherlands.
Magda A
MA
Świątek-Połatyńska
Molecular Biotechnology, Institute of Biology Leiden, Leiden University, Leiden, The Netherlands.
Joost
J
Willemse
InBioS - Centre for Protein Engineering, Université de Liège, Institut de Chimie B6a, Liège, Belgium.
Elodie
E
Tenconi
InBioS - Centre for Protein Engineering, Université de Liège, Institut de Chimie B6a, Liège, Belgium.
Sébastien
S
Rigali
Molecular Genetics, Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
Nora
N
Goosen
Microbial Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, United Kingdom.
Colin P
CP
Smith
Molecular Biotechnology, Institute of Biology Leiden, Leiden University, Leiden, The Netherlands.
Gilles P
0000-0003-0341-1561
GP
van Wezel
Developmental control; Streptomyces; dormancy; stress response