OsdR of Streptomyces coelicolor and the Dormancy Regulator DevR of Mycobacterium tuberculosis Control Overlapping Regulons

Abstract

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 Mycobacterium tuberculosis. In mycobacteria, dormancy is controlled by the response regulator DevR, which responds to conditions of hypoxia. Here, we show that OsdR of Streptomyces coelicolor 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 dosR and osdR is conserved between M. tuberculosis and S. 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.

Anaerobic nitrate respiration in the aerobe Streptomyces coelicolor A3(2): helping maintain a proton gradient during dormancy

“…Despite also being active in mycelium under hypoxic and anoxic conditions, Nar2 is not completely reliant on the bcc‐aa 3 ‐supercomplex for activity (Falke et al ., ). A further difference between the two systems is that hypoxia also induces transcription of the narG2H2J2I2 operon and this is completely dependent on the OsdKR two‐component system ( o xygen, s tress and d evelopment) in mycelium: OsdK is a membrane‐associated histidine kinase and OsdR a predicted DNA‐binding response regulator (Urem et al ., ; Fischer et al ., ). The presumptive osdRK operon is located in the neighbourhood of the nar2 operon in S. coelicolor (Fischer et al ., ) and the regulon controlled by OsdKR is extensive and includes a number of genes and operons encoding stress‐related as well as dormancy proteins (Urem et al ., ).…”

“…A further difference between the two systems is that hypoxia also induces transcription of the narG2H2J2I2 operon and this is completely dependent on the OsdKR two‐component system ( o xygen, s tress and d evelopment) in mycelium: OsdK is a membrane‐associated histidine kinase and OsdR a predicted DNA‐binding response regulator (Urem et al ., ; Fischer et al ., ). The presumptive osdRK operon is located in the neighbourhood of the nar2 operon in S. coelicolor (Fischer et al ., ) and the regulon controlled by OsdKR is extensive and includes a number of genes and operons encoding stress‐related as well as dormancy proteins (Urem et al ., ). Amongst these is the gene encoding the Nar2‐specific nitrate: nitrite antiporter NarK2, without which nitrate cannot be delivered to the cytoplasmically oriented active site of Nar2, nor can the toxic product of the reaction, nitrite, be exported from the mycelium (Fischer et al ., ).…”

Multiscale heterogeneity in filamentous microbes

“…Other 499 stress-related proteins being overrepresented in the population of large pellets include 500 polypeptides encoded by genes in the osdR locus, including the gene for the universal stress 501 protein (USP) (SCO0200) (van Veluw et al, 2012). Recent studies revealed that osdR controls 502 development and oxidative stress, and is functionally similar to DosR, the oxygen-sensitive 503 dormancy response regulator in Mycobacterium tuberculosis (Urem et al, 2016). It is 504 interesting to mention that the classes of genes being differently expressed in Streptomyces 505 pellets are known to be subject to transcriptional noise in other microbes (see above).…”

Translational control plays an important role in the adaptive heat-shock response of Streptomyces coelicolor

“…It is known that SCO0200 is under the control of the OsdR/OsdS two component system in S. coelicolor, the functional orthologue of the DevR/DevS of Mycobacterium tuberculosis which controls the dormancy response for surviving the host defence mechanism. The OsdR/OsdS system in Streptomyces has evolved a different role in controlling stress and developmental genes to coordinate the onset of morphological development and antibiotic production in response to environmental conditions 33 . Cluster 3 includes four ATP transporter ATP-binding proteins (AAA+ATPases) also involved in defense mechanisms: SCO3089, SCO3111, SCO3956 and SCO3958.…”

“…These include a batch of 'universal stress response' proteins and ABC transporters and, notably, 14 of these translationally-induced genes are contained within a 50-gene segment of the 'redox stress response' cluster (SCO0162-SCO0212) close to one end of the chromosome 33,34 . These gene products are considered to play a critical role in stress adaptation because the genes are induced only at the level of translation, avoiding the requirement for additional transcription; this regulatory strategy ensures a near instantaneous response to the environmental stressor.…”