Genome-wide analysis of the role of the antibiotic biosynthesis regulator AbsA2 in Streptomyces coelicolor A3(2)

Lewis, Richard A.; Wahab, Abdul; Bucca, Giselda; Laing, Emma; Möller-Levet, Carla S.; Kierzek, Andrzej; Smith, Colin P.

doi:10.1371/journal.pone.0200673

Cited by 10 publications

(9 citation statements)

References 36 publications

(65 reference statements)

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“…The regulator RedZ is at the top of the regulatory cascade governing expression of the genes involved in prodiginine biosynthesis. Multiple regulators are known to influence redZ expression, including DasR (59), ScbR2 (60), and GlnR (61), among others (62)(63)(64). These regulators sense N-acetylglucosamine, antibiotics (including prodiginines and actinorhodin), and cellular nitrogen levels, respectively.…”

Section: Discussionmentioning

confidence: 99%

Genetic Network Architecture and Environmental Cues Drive Spatial Organization of Phenotypic Division of Labor in Streptomyces coelicolor

Zacharia

Sue

et al. 2021

mBio

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A number of bacteria are known to differentiate into cells with distinct phenotypic traits during processes such as biofilm formation or the development of reproductive structures. These cell types, by virtue of their specialized functions, embody a division of labor. However, how bacteria build spatial patterns of differentiated cells is not well understood. Here, we examine the factors that drive spatial patterns in divisions of labor in colonies of Streptomyces coelicolor, a multicellular bacterium capable of synthesizing an array of antibiotics and forming complex reproductive structures (e.g., aerial hyphae and spores). Using fluorescent reporters, we demonstrate that the pathways for antibiotic biosynthesis and aerial hypha formation are activated in distinct waves of gene expression that radiate outwards in S. coelicolor colonies. We also show that the spatiotemporal separation of these cell types depends on a key activator in the developmental pathway, AdpA. Importantly, when we manipulated local gradients by growing competing microbes nearby, or through physical disruption, expression in these pathways could be decoupled and/or disordered, respectively. Finally, the normal spatial organization of these cell types was partially restored with the addition of a siderophore, a public good made by these organisms, to the growth medium. Together, these results indicate that spatial divisions of labor in S. coelicolor colonies are determined by a combination of physiological gradients and regulatory network architecture, key factors that also drive patterns of cellular differentiation in multicellular eukaryotic organisms. IMPORTANCE Streptomyces coelicolor is a multicellular bacterium that differentiates into specialized cell types and produces a diverse array of natural products. While much is known about the genetic networks that regulate development and antibiotic biosynthesis in S. coelicolor, what drives the spatial organization of these activities within a colony remains to be explored. By using time-lapse microscopy to monitor gene expression in developmental and antibiotic biosynthesis pathways, we found that expression in these pathways occurs in spatiotemporally separated waves. Normally, expression of the antibiotic biosynthesis pathway preceded expression in the developmental pathway; however, this order was compromised in a mutant lacking a key developmental regulator. Furthermore, when we disrupted the local gradients during S. coelicolor growth, we observed disordered patterns of gene expression within colonies. Together, these results indicate that spatial divisions of labor in S. coelicolor colonies are determined by a combination of regulatory network architecture and physiological gradients.

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Section: Discussionmentioning

confidence: 99%

Genetic Network Architecture and Environmental Cues Drive Spatial Organization of Phenotypic Division of Labor in Streptomyces coelicolor

Zacharia

Sue

et al. 2021

mBio

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“… 2017 ) and antibiotic biosynthesis (Sheeler, MacMillan and Nodwell 2005 ; Lewis et al . 2019 ), such as mtrA / mtrB and absA1 / absA2 , respectively. In addition, the presence of nutrients such as N-acetylglucosamine derived from chitin prevents the activation of redZ through the action of DasR (Rigali et al .…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of undecylprodigiosin biosynthesis in the yeast-scavenging Streptomyces strain MBK6

Baral

Siitonen

Laughlin

et al. 2021

FEMS Microbiology Letters

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Streptomyces are efficient chemists with a capacity to generate diverse and potent chemical scaffolds. The secondary metabolism of these soil-dwelling prokaryotes is stimulated upon interaction with other microbes in their complex ecosystem. We observed such an interaction when a Streptomyces isolate was cultivated in a media supplemented with dead yeast cells. Whole-genome analysis revealed that Streptomyces sp. MBK6 harbours the red cluster that is cryptic under normal environmental conditions. An interactive culture of MBK6 with dead yeast triggered the production of the red pigments metacycloprodigiosin and undecylprodigiosin. Streptomyces sp. MBK6 scavenges dead-yeast cells and preferentially grows in aggregates of sequestered yeasts within its mycelial network. We identified that the activation depends on the cluster-situated regulator, mbkZ, which may act as a cross-regulator. Cloning of this master regulator mbkZ in S. coelicolor with a constitutive promoter and promoter-deprived conditions generated different production levels of the red pigments. These surprising results were further validated by DNA-protein binding assays. The presence of the red cluster in Streptomyces sp. MBK6 provides a vivid example of horizontal gene transfer of an entire metabolic pathway followed by differential adaptation to a new environment through mutations in the receiver domain of the key regulatory protein MbkZ.

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“…This TCS was one of the first regulators of antibiotic production described in [ 51 ]. This system has been established as a negative regulator of the production of the antibiotics ACT, RED, and CDA [ 52 , 53 , 54 , 55 , 56 ], through the direct regulation of the specific regulators of the synthesis pathways actII-ORF4 , redZ, and cdaR [ 55 , 57 ]. In the case of the regulation of CDA synthesis, it has been observed that AbsA2 is also able to directly regulate several genes of the cda cluster [ 55 ].…”

Section: Two-component Systems Of Streptomyces Coelicolormentioning

confidence: 99%

Two-Component Systems of Streptomyces coelicolor: An Intricate Network to Be Unraveled

Nieta

Santamaría

Díaz

2022

IJMS

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Bacteria of the Streptomyces genus constitute an authentic biotech gold mine thanks to their ability to produce a myriad of compounds and enzymes of great interest at various clinical, agricultural, and industrial levels. Understanding the physiology of these organisms and revealing their regulatory mechanisms is essential for their manipulation and application. Two-component systems (TCSs) constitute the predominant signal transduction mechanism in prokaryotes, and can detect a multitude of external and internal stimuli and trigger the appropriate cellular responses for adapting to diverse environmental conditions. These global regulatory systems usually coordinate various biological processes for the maintenance of homeostasis and proper cell function. Here, we review the multiple TCSs described and characterized in Streptomyces coelicolor, one of the most studied and important model species within this bacterial group. TCSs are involved in all cellular processes; hence, unravelling the complex regulatory network they form is essential for their potential biotechnological application.

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Genome-wide analysis of the role of the antibiotic biosynthesis regulator AbsA2 in Streptomyces coelicolor A3(2)

Cited by 10 publications

References 36 publications

Genetic Network Architecture and Environmental Cues Drive Spatial Organization of Phenotypic Division of Labor in Streptomyces coelicolor

Genetic Network Architecture and Environmental Cues Drive Spatial Organization of Phenotypic Division of Labor in Streptomyces coelicolor

Differential regulation of undecylprodigiosin biosynthesis in the yeast-scavenging Streptomyces strain MBK6

Two-Component Systems of Streptomyces coelicolor: An Intricate Network to Be Unraveled

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