Identification of a novel two-component system SenS/SenR modulating the production of the catalase-peroxidase CpeB and the haem-binding protein HbpS in Streptomyces reticuli

Abstract

The Gram-positive soil bacterium and cellulose degraderStreptomyces reticulisynthesizes the mycelium-associated enzyme CpeB, which displays haem-dependent catalase and peroxidase activity, as well as haem-independent manganese-peroxidase activity. The expression of thefurS–cpeBoperon depends on the redox regulator FurS and the presence of the haem-binding protein HbpS. Upstream ofhbpS, the neighbouringsenSandsenRgenes were identified. SenS is a sensor histidine kinase with five predicted N-terminally located transmembrane domains. SenR is the corresponding response regulator with a C-terminal DNA-binding motif. Comparative transcriptional and biochemical studies with a designedS. reticuli senS/senRchromosomal disruption mutant and a set of constructedStreptomyces lividanstransformants showed that the presence of the novel two-component system SenS/SenR negatively modulates the expression of thefurS–cpeBoperon and thehbpSgene. The presence of SenS/SenR enhances considerably the resistance ofS. reticulito haemin and the redox-cycling compound plumbagin, suggesting that this system could participate directly or indirectly in the sensing of redox changes. Epitope-tagged HbpS (obtained from anEscherichia colitransformant) as well as the nativeS. reticuliHbpS interactin vitrospecifically with the purified SenS fusion protein. On the basis of these findings, together with data deduced from theS. reticuli hbpSmutant strain, HbpS is suggested to act as an accessory protein that communicates with the sensor protein to modulate the corresponding regulatory cascade. Interestingly, close and distant homologues, respectively, of the SenS/SenR system are encoded within theStreptomyces coelicolorA3(2) andStreptomyces avermitilisgenomes, but not within other known bacterial genomes. Hence the SenS/SenR system appears to be confined to streptomycetes.