Extracellular sugar phosphates are assimilated by Streptomyces in a PhoP-dependent manner

Tenconi, Elodie; Jourdan, Samuel; Motté, Patrick; Rigali, Sébastien

doi:10.1007/s10482-012-9763-6

Cited by 19 publications

(20 citation statements)

References 34 publications

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“…Additionally, phospho6sugars inhibit antibiotic production in streptomycetes. This effect is mediated by the phosphate6 rather than of the glyco6moiety, as the inactivation of phoP or ppk prevents or enhances, respectively, their utilization as nutrient sources and their inhibitory effect on antibiotic production 224 .…”

Section: Connections Between Phosphate Nitrogen and Carbon Metabolismmentioning

confidence: 99%

Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era

et al. 2018

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Covering: 2000 to 2018 The antimicrobial activity of many of their natural products has brought prominence to the Streptomycetaceae, a family of Gram-positive bacteria that inhabit both soil and aquatic sediments. In the natural environment, antimicrobial compounds are likely to limit the growth of competitors, thereby offering a selective advantage to the producer, in particular when nutrients become limited and the developmental programme leading to spores commences. The study of the control of this secondary metabolism continues to offer insights into its integration with a complex lifecycle that takes multiple cues from the environment and primary metabolism. Such information can then be harnessed to devise laboratory screening conditions to discover compounds with new or improved clinical value. Here we provide an update of the review we published in NPR in 2011. Besides providing the essential background, we focus on recent developments in our understanding of the underlying regulatory networks, ecological triggers of natural product biosynthesis, contributions from comparative genomics and approaches to awaken the biosynthesis of otherwise silent or cryptic natural products. In addition, we highlight recent discoveries on the control of antibiotic production in other Actinobacteria, which have gained considerable attention since the start of the genomics revolution. New technologies that have the potential to produce a step change in our understanding of the regulation of secondary metabolism are also described.

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Section: Connections Between Phosphate Nitrogen and Carbon Metabolismmentioning

confidence: 99%

Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era

et al. 2018

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“…GlcNAc-dependent nutritional signaling is most likely mediated through changes in the intracellular level of GlcN-6-P, which binds as a ligand to the GntR-family regulator DasR, leading to derepression of DasR-mediated control of antibiotic production (Rigali et al, 2008). Recent work showed that addition of phosphorylated sugars to growth media under phosphate limitation delays the occurrence of the second round of PCD and results in vegetative arrest, also preventing antibiotic production (Tenconi, Jourdan, Motte, Virolle, & Rigali, 2012).…”

Section: Pcd and Antibiotic Productionmentioning

confidence: 99%

Morphogenesis of Streptomyces in Submerged Cultures

Dissel

Claessen

Wezel

2014

Advances in Applied Microbiology

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Members of the genus Streptomyces are mycelial bacteria that undergo a complex multicellular life cycle and propagate via sporulation. Streptomycetes are important industrial microorganisms, as they produce a plethora of medically relevant natural products, including the majority of clinically important antibiotics, as well as a wide range of enzymes with industrial application. While development of Streptomyces in surface-grown cultures is well studied, relatively little is known of the parameters that determine morphogenesis in submerged cultures. Here, growth is characterized by the formation of mycelial networks and pellets. From the perspective of industrial fermentations, such mycelial growth is unattractive, as it is associated with slow growth, heterogeneous cultures, and high viscosity. Here, we review the current insights into the genetic and environmental factors that determine mycelial growth and morphology in liquid-grown cultures. The genetic factors include cell-matrix proteins and extracellular polymers, morphoproteins with specific roles in liquid-culture morphogenesis, with the SsgA-like proteins as well-studied examples, and programmed cell death. Environmental factors refer in particular to those dictated by process engineering, such as growth media and reactor set-up. These insights are then integrated to provide perspectives as to how this knowledge can be applied to improve streptomycetes for industrial applications.

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“…SYTO9 and SYTOX stained samples were examined at a wavelength of 488 for excitation and 530 nm (green) for emission. Red autofluorescence of PdGs and propidium iodide-stained samples were examined at a wavelength of 543 nm (Leica TCS-SP2) or 568 nm (Leica TCS-SP5) for excitation and 630 nm (red) for emission as described previously (64).…”

Section: In Situ Visualization By Confocal Fluorescence Microscopymentioning

confidence: 99%

Prodiginine Production inStreptomyces coelicolorCorrelates Temporally and Spatially to Programmed Cell Death

Tenconi

Traxler

Hoebreck

et al. 2018

Preprint

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Programmed cell death (PCD) is a common feature of multicellularity and morphogenesis in bacteria. While cell death has been well documented when Streptomyces species switch from vegetative (nutrition) to aerial (reproduction) growth, lethal determinants are yet to be discovered to unveil the genetic basis of PCD in mycelial bacteria. In this work we used prodiginines of Streptomyces coelicolor as model to test the hypothesis that a bacterium uses 'self-made' antiproliferative DNA-damaging agents as toxins of their PCD process. Spatiotemporal visualisation of the autofluorescence of prodiginines reveals that their biosynthesis is triggered in the dying zone of the colony prior to morphological differentiation of the mycelium.A prodiginine nonproducer showed hyper-accumulation of viable filaments, with increased RNA and proteins synthesis when most of the mycelium of the wild-type strain was dead when prodiginine accumulated. Addition of a prodiginine synthesis inhibitor also strongly favoured viable over dead filaments. As self-toxicity has also been reported for other producers of DNAdamaging agents we propose that cytotoxic metabolites synthetized during the morphological transition of filamentous bacteria may be used to execute PCD. Significance StatementActinobacteria are prolific producers of compounds with antiproliferative activity, but why these bacteria synthetize metabolites with this bioactivity has so far remained a mystery. Using prodiginines (PdGs) as model system, we revealed that the spatio-temporal synthesis of these molecules correlates to cell death of the producer Streptomyces coelicolor and that inhibition of their synthesis results in hyper-accumulation of viable filaments. Since PdGs potentiate death of S. coelicolor recurrently prior to morphological differentiation, this is a form of programmed cell death (PCD). Hence, next to weapons in competition between organisms or signals in interand intra-species communications, we propose a third role for secondary metabolites i.e., elements required for self-toxicity in PCD processes.

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Extracellular sugar phosphates are assimilated by Streptomyces in a PhoP-dependent manner

Cited by 19 publications

References 34 publications

Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era

Regulation of antibiotic production in Actinobacteria: new perspectives from the post-genomic era

Morphogenesis of Streptomyces in Submerged Cultures

Prodiginine Production inStreptomyces coelicolorCorrelates Temporally and Spatially to Programmed Cell Death

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