c-di-GMP signalling and the regulation of developmental transitions in streptomycetes

Bush, Matthew J.; Tschowri, Natalia; Schlimpert, Susan; Flärdh, Klas; Buttner, Mark J.

doi:10.1038/nrmicro3546

Cited by 159 publications

(204 citation statements)

References 105 publications

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“…BldD is located at the top of the regulatory hierarchy that controls morphological differentiation in Streptomyces species, serving as the transcriptional repressor of sporulation genes (8). In this study, we showed that the BldD orthologue AmBldD plays an important role in the morphological differentiation of A. missouriensis.…”

Section: Discussionmentioning

confidence: 64%

Regulation of Sporangium Formation by BldD in the Rare Actinomycete Actinoplanes missouriensis

et al. 2017

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The rare actinomycete Actinoplanes missouriensis forms sporangia, including hundreds of flagellated spores that start swimming as zoospores after their release. Under conditions suitable for vegetative growth, zoospores stop swimming and germinate. A comparative proteome analysis between zoospores and germinating cells identified 15 proteins that were produced in larger amounts in germinating cells. They include an orthologue of BldD (herein named AmBldD [BldD of A. missouriensis]), which is a transcriptional regulator involved in morphological development and secondary metabolism in Streptomyces. AmBldD was detected in mycelia during vegetative growth but was barely detected in mycelia during the sporangiumforming phase, in spite of the constant transcription of AmbldD throughout growth. An AmbldD mutant started to form sporangia much earlier than the wild-type strain, and the resulting sporangia were morphologically abnormal. Recombinant AmBldD bound a palindromic sequence, the AmBldD box, located upstream from AmbldD. 3=,5=-Cyclic di-GMP significantly enhanced the in vitro DNA-binding ability of AmBldD. A chromatin immunoprecipitation-sequencing analysis and an in silico search for AmBldD boxes revealed that AmBldD bound 346 genomic loci that contained the 19-bp inverted repeat 5=-NN(G/A)TNACN(C/G)N(G/C)NGTNA(C/T)NN-3= as the consensus AmBldDbinding sequence. The transcriptional analysis of 27 selected AmBldD target gene candidates indicated that AmBldD should repress 12 of the 27 genes, including bldM, ssgB, whiD, ddbA, and wblA orthologues. These genes are involved in morphological development in Streptomyces coelicolor A3(2). Thus, AmBldD is a global transcriptional regulator that seems to repress the transcription of tens of genes during vegetative growth, some of which are likely to be required for sporangium formation.IMPORTANCE The rare actinomycete Actinoplanes missouriensis undergoes complex morphological differentiation, including sporangium formation. However, almost no molecular biological studies have been conducted on this bacterium. BldD is a key global regulator involved in the morphological development of streptomycetes. BldD orthologues are highly conserved among sporulating actinomycetes, but no BldD orthologues, except one in Saccharopolyspora erythraea, have been studied outside the streptomycetes. Here, it was revealed that the BldD orthologue AmBldD is essential for normal developmental processes in A. missouriensis. The AmBldD regulon seems to be different from the BldD regulon in Streptomyces coelicolor A3(2), but they share four genes that are involved in morphological differentiation in S. coelicolor A3(2).KEYWORDS gene regulation, rare actinomycete, regulon, sporangium formation, transcriptional factor A ctinomycetes are Gram-positive, mainly soil-inhabiting bacteria. Many genera of actinomycetes show filamentous growth and produce spores, and therefore, actinomycetes are generally characterized by a complex morphological development. For

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Section: Discussionmentioning

confidence: 64%

Regulation of Sporangium Formation by BldD in the Rare Actinomycete Actinoplanes missouriensis

et al. 2017

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“…Whether additional electron shuttle-producing microbes, or those that exploit the shuttles produced by others, have the capacity to control social behavior during this process is not known. However, as electron shuttle production and utilization is observed in phylogenetically disparate organisms (3,12), and developmental regulation by the secondary messenger c-di-GMP is a common bacterial trait (20,47), similar mechanisms could be operating in multicellular communities formed by diverse microbes.…”

Section: Colony Matrix Distribution Phenotypes Suggest That Phenazinementioning

confidence: 99%

Electron-shuttling antibiotics structure bacterial communities by modulating cellular levels of c-di-GMP

Okegbe

Fields

Cole

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

101

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Diverse organisms secrete redox-active antibiotics, which can be used as extracellular electron shuttles by resistant microbes. Shuttlemediated metabolism can support survival when substrates are available not locally but rather at a distance. Such conditions arise in multicellular communities, where the formation of chemical gradients leads to resource limitation for cells at depth. In the pathogenic bacterium Pseudomonas aeruginosa PA14, antibiotics called phenazines act as oxidants to balance the intracellular redox state of cells in anoxic biofilm subzones. PA14 colony biofilms show a profound morphogenic response to phenazines resulting from electron acceptor-dependent inhibition of ECM production. This effect is reminiscent of the developmental responses of some eukaryotic systems to redox control, but for bacterial systems its mechanistic basis has not been well defined. Here, we identify the regulatory protein RmcA and show that it links redox conditions to PA14 colony morphogenesis by modulating levels of bis-(3′,5′)-cyclic-dimeric-guanosine (c-di-GMP), a second messenger that stimulates matrix production, in response to phenazine availability. RmcA contains four Per-Arnt-Sim (PAS) domains and domains with the potential to catalyze the synthesis and degradation of c-di-GMP. Our results suggest that phenazine production modulates RmcA activity such that the protein degrades c-di-GMP and thereby inhibits matrix production during oxidizing conditions. RmcA thus forms a mechanistic link between cellular redox sensing and community morphogenesis analogous to the functions performed by PAS-domain-containing regulatory proteins found in complex eukaryotes.W hen microbial cells cannot import or are physically separated from metabolic electron donors or acceptors, diffusible compounds can act as electron carriers and support survival on these substrates (1, 2). These conditions arise in the presence of poised-potential electrodes or insoluble minerals, such as iron oxides (3-5), and in multicellular communities (biofilms) where the formation of chemical gradients leads to oxidant limitation for cells at depth (6-9). Diverse microbes secrete redoxactive compounds with the capacity to function as electron shuttles (10-12). In the pathogenic bacterium Pseudomonas aeruginosa PA14, electron-shuttling antibiotics called phenazines support survival on poised-potential electrodes and balance the intracellular redox state of cells in anoxic biofilm subzones (1, 9).Similar to those formed by many species of microbes, colonies of PA14 develop intricate wrinkle structures on agar-solidified growth media (13). Phenazines profoundly alter PA14 colony morphogenesis, inhibiting the onset of wrinkle formation and changing the organization of wrinkles (12) (Fig. 1A). Modeling of resource availability within colonies suggests that the earlier increase in the colony surface area-to-volume ratio in phenazine-null (Δphz) mutants maximizes access to oxygen for cells that would otherwise become limited for oxidant (14). Measurements of...

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“…Streptomycetes are filamentous, antibiotic-producing soil bacteria that have a multicellular life cycle with two distinct modes of cell division: vegetative cross-wall formation and sporulation septation (11) (Fig. 1A).…”

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confidence: 99%

Two dynamin-like proteins stabilize FtsZ rings during Streptomyces sporulation

Schlimpert

Wasserström

Chandra

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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During sporulation, the filamentous bacteria Streptomyces undergo a massive cell division event in which the synthesis of ladders of sporulation septa convert multigenomic hyphae into chains of unigenomic spores. This process requires cytokinetic Z-rings formed by the bacterial tubulin homolog FtsZ, and the stabilization of the newly formed Z-rings is crucial for completion of septum synthesis. Here we show that two dynamin-like proteins, DynA and DynB, play critical roles in this process. Dynamins are a family of large, multidomain GTPases involved in key cellular processes in eukaryotes, including vesicle trafficking and organelle division. Many bacterial genomes encode dynamin-like proteins, but the biological function of these proteins has remained largely enigmatic. Using a cell biological approach, we show that the two Streptomyces dynamins specifically localize to sporulation septa in an FtsZ-dependent manner. Moreover, dynamin mutants have a cell division defect due to the decreased stability of sporulation-specific Z-rings, as demonstrated by kymographs derived from time-lapse images of FtsZ ladder formation. This defect causes the premature disassembly of individual Z-rings, leading to the frequent abortion of septum synthesis, which in turn results in the production of long spore-like compartments with multiple chromosomes. Two-hybrid analysis revealed that the dynamins are part of the cell division machinery and that they mediate their effects on Z-ring stability during developmentally controlled cell division via a network of protein-protein interactions involving DynA, DynB, FtsZ, SepF, SepF2, and the FtsZ-positioning protein SsgB.he active organization and remodeling of cellular membranes is a fundamental process for all organisms. Many of these remodeling events involve the reshaping, fission, or fusion of lipid bilayers to generate new organelles, release transport vesicles, or stabilize specific membrane structures. In eukaryotes, key cellular processes, such as the fission and fusion of mitochondria, the division of chloroplasts, endocytosis, and viral resistance, are mediated by members of the dynamin superfamily (1). Dynamins and dynamin-like proteins are mechanochemical GTPases that polymerize into helical scaffolds at the surface of membranes. GTP hydrolysis is coupled to a radical conformational change in the protein structure that forces the underlying lipid layer into an energetically unstable conformation that promotes membrane rearrangements, probably via a hemifusion intermediate (2, 3).Dynamin-like proteins are found in many bacterial species, yet the precise roles of these proteins are still largely unknown. They share a conserved domain architecture with the canonical human Dynamin 1, including the N-terminal GTPase domain, a neck domain involved in dynamin dimerization, and a trunk domain involved in stimulation of GTPase activity (4, 5). In contrast, bacterial dynamins lack the pleckstrin homology motif and proline-rich sequences found in classical dynamins and contain instead o...

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c-di-GMP signalling and the regulation of developmental transitions in streptomycetes

Cited by 159 publications

References 105 publications

Regulation of Sporangium Formation by BldD in the Rare Actinomycete Actinoplanes missouriensis

Regulation of Sporangium Formation by BldD in the Rare Actinomycete Actinoplanes missouriensis

Electron-shuttling antibiotics structure bacterial communities by modulating cellular levels of c-di-GMP

Two dynamin-like proteins stabilize FtsZ rings during Streptomyces sporulation

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