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 in , allowing this pathogen to escape the host defense system. Here, we show that OsdR (SCO0204) of the soil bacterium is a functional orthologue of DevR. OsdR, when activated by the sensory kinase OsdK (SCO0203), binds upstream of the DevR-controlled dormancy genes , , and Rv3134c of . analysis of the genome combined with DNA binding studies identified many binding sites in the genomic region around itself 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 the mutant. A peak in transcription 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. Dormancy 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 from . In mycobacteria, dormancy is controlled by the response regulator DevR, which responds to conditions of hypoxia. Here, we show that OsdR of recognizes 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 of and is conserved between and , 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.
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http://dx.doi.org/10.1128/mSystems.00014-16 | DOI Listing |
BMC Microbiol
October 2023
Department of Bioscience, Faculty of Life Sciences, Tokyo University of Agriculture, Sakuragaoka, Tokyo, Setagaya-Ku, 156-8502, Japan.
Background: Previous studies have revealed a nitric oxide (NO) metabolic cycle in which NO, nitrate (NO), and nitrite (NO) circulate. The NO produced in this cycle serves as a signalling molecule that regulates actinorhodin (ACT) production via the DevS/DevR NO-dependent two-component system (TCS) in Streptomyces coelicolor A3(2) M145. However, the mechanisms involved in the regulation of NO signalling in S.
View Article and Find Full Text PDFFEMS Microbiol Lett
January 2023
Faculty of Life Sciences, Department of Bioscience, Tokyo University of Agriculture, 1-1-1 Sakuragaoka Setagaya-ku, Tokyo 1568502, Japan.
Our previous studies revealed that a two-component system (TCS), DevS, and DevR, regulate both nitric oxide (NO) signaling and NO homeostasis in the actinobacterium Streptomyces coelicolor A3(2) M145, suggesting a reasonable system for NO-dependent metabolism. In this study, sequence alignment of DevR and DevR homologs found Asp66 (D66) and Thr196 (T196) as predicted phosphorylation sites of DevR. Phos-tag gel electrophoretic mobility shift assay suggested that D66 and T196 are involved in the phosphorylation of DevR.
View Article and Find Full Text PDFACS Infect Dis
December 2022
Department of Biotechnology, All India Institute of Medical Sciences, New Delhi110029, India.
Tuberculosis is recognized as one of the major public health threats worldwide. The DevR-DevS (DosR/DosS) two-component system is considered a novel drug target in (Mtb), the etiological agent of tuberculosis, owing to its central role in bacterial adaptation and long-term persistence. An increase in DevR levels and the decreased permeability of the mycobacterial cell wall during hypoxia-associated dormancy pose formidable challenges to the development of anti-DevR compounds.
View Article and Find Full Text PDFBiochem J
August 2021
Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi, India.
DevR/DosR response regulator is believed to participate in virulence, dormancy adaptation and antibiotic tolerance mechanisms of Mycobacterium tuberculosis by regulating the expression of the dormancy regulon. We have previously shown that the interaction of DevR with RNA polymerase is essential for the expression of DevR-regulated genes. Here, we developed a M.
View Article and Find Full Text PDFAppl Environ Microbiol
June 2021
Faculty of Life Sciences, Department of Bioscience, Tokyo University of Agriculture, Tokyo, Japan.
Nitric oxide (NO) is an important signaling molecule in eukaryotic and prokaryotic cells. A previous study revealed an NO synthase-independent NO production metabolic cycle in which the three nitrogen oxides, nitrate (NO), nitrite (NO), and NO, were generated in the actinobacterium Streptomyces coelicolor A3(2). NO was suggested to act as a signaling molecule, functioning as a hormone that regulates secondary metabolism.
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