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A meet-up of AcP and c-di-GMP modulates BldD activity for development and antibiotic production in actinobacteria

ABSTRACT: Actinobacteria are ubiquitous bacteria undergoing complex developmental transition coincided with antibiotics production in response to stress or nutrients starvation. This transition is mainly controlled by the interaction between the second messenger c-di-GMP and the master repressor BldD. To date, the upstream factors and the global signal networks that regulate this intriguing cell biological processes still remained unknown. In Saccharopolyspora erythraea, we found that acetyl phosphate (AcP) accumulation resulting from environmental nitrogen stress participated in the regulation of BldD activity through cooperation with c-di-GMP. AcP-induced acetylation of BldD at K11 caused the BldD dimer to fall apart and dissociate from the target DNA, as well as disrupted the signal transduction of c-di-GMP, thus governed both developmental transition and antibiotics production. Meanwhile, practical mutation of BldDK11R bypassing the acetylation regulation could enhance the positive effect of BldD on antibiotics production. Our finding represents an entirely different role of the covalent modification caused by AcP, which integrated with c-di-GMP signal in modulating the activity of BldD for development and antibiotic production coping with environmental stress. This coherent and highly conserved regulatory network might offer new insight into the direct connections from specific regulator to the actinobacteria biological process associated with major morphogenetic event

ORGANISM(S): Saccharopolyspora erythraea

PROVIDER: GSE225241 | GEO | 2023/08/08

REPOSITORIES: GEO

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Comparison of Expression Profiles for Agrobacterium tumefaciens visR mutant to wild-type strain.

Project description:Many bacteria colonize surfaces and transition to a sessile mode of growth. The plant pathogen Agrobacterium tumefaciens produces a unipolar polysaccharide (UPP) adhesin at single cell poles that contact surfaces. Here we report that elevated levels of the intracellular signal cyclic diguanosine monophosphate (c-di-GMP) lead to surface-contact-independent UPP production and a red colony phenotype due to production of UPP and the exopolysaccharide cellulose, when A. tumefaciens is incubated with the polysaccharide stain Congo Red. Transposon mutations with elevated Congo Red staining identified presumptive UPP-negative regulators, mutants for which were hyperadherent, producing UPP irrespective of surface contact. Multiple independent mutations were obtained in visN and visR, activators of flagellar motility in A. tumefaciens, now found to inhibit UPP and cellulose production. Expression analysis in a visR mutant and isolation of suppressor mutations, identified three diguanylate cyclases inhibited by VisR. Null mutations for two of these genes decrease attachment and UPP production, but do not alter cellular c-di-GMP levels. However, analysis of catalytic site mutants revealed their GGDEF motifs are required to increase UPP production and surface attachment. Mutations in a specific presumptive c-di-GMP phosphodiesterase also elevate UPP production and attachment, consistent with c-di-GMP activation of surface-dependent adhesin deployment. Three biological replicates, independent RNA preparations, one dye swap.

2014-08-21 | E-GEOD-60565 | biostudies-arrayexpress

Allosteric regulation by c-di-AMP modulates global signal integration in Actinobacteria

Project description:C-di-AMP is primarily associated with the regulation of carbon utilization as well as other central traits, central metabolism, and bacterial stringent response to environmental changes. Elevated c-di-AMP levels result in aberrant physiology for most c-di-AMP synthesizing organisms, drawing particular attention to the importance of the c-di-AMP homeostasis and the molecular mechanisms pertaining to nucleotide metabolism and signal transduction. Here we show that c-di-AMP binds the GntR-family regulator DasR, uncovering a direct link between c-di-AMP and GlcNAc signaling. Further, we show c-di-AMP functions as an allosteric activator of DasR activity. GlcNAc is necessary for cell-surface structure from bacteria to humans, as well as a signal for bacterial development and antibiotic production. DasR is a global repressor that oversees GlcNAc metabolism and antibiotic production, which enables Actinobacteria to cope with stress and starvation. Our in vivo studies reveal the important biological role of allosteric regulation by c-di-AMP in metabolic imbalance and the transduction of a series of signals. Notably, DasR also controls intracellular c-di-AMP level through direct repression on disA. Overall, we identify a function of allosteric regulation between c-di-AMP and DasR in global signal integration and c-di-AMP homeostasis in bacteria, which is likely widespread in Actinobacteria.

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Comparison of Expression Profiles for Agrobacterium tumefaciens visR mutant to wild-type strain.

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2023-12-12 | MTBLS7053 | MetaboLights

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