Sébastien Rigali

• PhD
• FNRS - Maître de Recherche at University of Liège

Volatile compounds (VCs) produced by most host-associated bacteria remain largely unexplored despite their potential roles in suppressing microbial competitors and facilitating host colonization. This study investigated the volatilome of Streptomyces scabiei 87-22, the model species for causative agents of common scab in root and tuber crops, under...

Bacteria produce diverse bioactive metabolites with ecological and pharmaceutical importance. These compounds are synthesized by biosynthetic gene clusters (BGCs), whose expression is tightly regulated. While many studies have examined the factors influencing BGC expression, including transcription factors (TFs) and environmental signals, the regul...

Streptomyces scabiei is the causative agents of common scab on root and tuber crops. Life in the soil imposes intense competition between soil-dwelling microorganisms and we evaluated here the antimicrobial properties of S. scabiei. Under laboratory culture conditions, increasing peptone levels correlated with increased growth inhibitory properties...

The amino sugar N- acetylglucosamine (GlcNAc) plays a central role in primary metabolism and is a key signaling molecule for the onset of morphological and chemical differentiation of Streptomyces . The global nutrient-sensory regulator DasR acts as the gatekeeper of development in streptomycetes, and its activity is modulated by aminosugar phospha...

Actinobacteria undergo a complex multicellular life cycle and produce a wide range of specialized metabolites, including the majority of the antibiotics. These biological processes are controlled by intricate regulatory pathways, and to better understand how they are controlled we need to augment our insights into the transcription factor binding s...

Cyclic lipopeptides (CLPs) are key bioactive secondary metabolites produced by some plant beneficial rhizobacteria such as Pseudomonas and Bacillus. They exhibit antimicrobial properties, promote induced systemic resistance in plants, and support key developmental traits, including motility, biofilm formation, and root colonization. However, our kn...

In Streptomyces scabiei , the main causative agent of common scab disease of root and tuber crops, the interaction between the substrate-binding protein (SBP) CebE (CebE scab ) and cellotriose released by the plant host ( K D in the nanomolar range) is the first event for the onset of its pathogenic lifestyle. Here, we report the structure of CebE...

Cyclic lipopeptides are key bioactive secondary metabolites produced by some plant beneficial rhizobacteria such as Pseudomonas and Bacillus . They exhibit antimicrobial properties, promote induced systemic resistance in plants and support key developmental traits including motility, biofilm formation and root colonization. However, our knowledge a...

In Streptomyces scabiei , the main causative agent of common scab disease of root and tuber crops, the interaction between the substrate-binding protein (SBP) CebE (CebE scab ) and cellotriose released by the plant host ( K D in the nanomolar range) is the first event for the onset of its pathogenic lifestyle. Here we report the structure of CebE s...

Simple Summary The bacterium Streptomyces scabiei is the main causative agent of common scab disease on economically important root and tuber crops. Our work investigated if and how this pathogen uses multiple sugar transport systems to sense the presence of a living plant host through perception and import of cello-oligosaccharides, the elicitors...

Streptomyces lunaelactis strains have been isolated from moonmilk deposits, which are calcium carbonate speleothems used for centuries in traditional medicine for their antimicrobial properties. Genome mining revealed that these strains are a remarkable example of a Streptomyces species with huge heterogeneity regarding their content in biosyntheti...

Streptomyces lunaelactis strains have been isolated from moonmilk deposits which are calcium carbonate speleothems used for centuries in traditional medicine for their antimicrobial proper-ties. Genome mining revealed that these strains are a remarkable example of a Streptomyces spe-cies with huge heterogeneity regarding their content in biosynthet...

Plant decaying biomass is the most abundant provider of carbon sources for soil-dwelling microorganisms. To optimally evolve in such environmental niches, microorganisms possess an arsenal of hydrolytic enzymatic complexes to feed on the various types of polysaccharides, oligosaccharides, and monosaccharides.

Transcriptional regulation is key in bacteria for providing an adequate response in time and space to changing environmental conditions. However, despite decades of research, the binding sites and therefore the target genes and the function of most transcription factors (TFs) remain unknown. Filling this gap in knowledge through conventional method...

Ferroverdins are ferrous iron (Fe²⁺)-nitrosophenolato complexes produced by a few Streptomyces species as a response to iron overload. Previously, three ferroverdins were identified: ferroverdin A, in which three molecules of p-vinylphenyl-3-nitroso-4-hydroxybenzoate (p-vinylphenyl-3,4-NHBA) are recruited to bind Fe²⁺, and Ferroverdin B and Ferrove...

Transcriptional regulation is key in bacteria for providing an adequate response in time and space to changing environmental conditions. However, despite decades of research, the binding sites and therefore the target genes and the function of most transcription factors (TFs) remain unknown. Filling this gap in knowledge through conventional method...

Cellulose being the most abundant polysaccharide on earth, beta-glucosidases hydrolyzing cello-oligosaccharides are key enzymes to fuel glycolysis in microorganisms developing on plant material. In Streptomyces scabiei, the causative agent of common scab in root and tuber crops, a genetic compensation phenomenon safeguards the loss of the gene enco...

The development of spots or lesions symptomatic of common scab on root and tuber crops is caused by few pathogenic Strep-tomyces with Streptomyces scabiei 87-22 as the model species. Thaxtomin phytotoxins are the primary virulence determinants, mainly acting by impairing cellulose synthesis, and their production in S. scabiei is in turn boosted by...

The beta-glucosidase BglC fulfills multiple functions in both primary metabolism and induction of pathogenicity of Streptomyces scabiei, the causative agent of common scab in root and tuber crops. Indeed, this enzyme hydrolyzes cellobiose and cellotriose to feed glycolysis with glucose directly and modifies the intracellular concentration of these...

The beta-glucosidase BglC fulfills multiple functions in both primary metabolism and induction of pathogenicity of Streptomyces scabiei , the causative agent of the common scab disease of root and tuber crops. Indeed, this enzyme hydrolyzes cellobiose and cellotriose to directly feed glycolysis with glucose, but also modifies the intracellular conc...

The development of spots or lesions symptomatic of the common scab disease on root and tuber crops is caused by few pathogenic Streptomyces with Streptomyces scabiei 87-22 as the model species. Thaxtomin phytotoxins are the primary virulence determinants, mainly acting by impairing cellulose synthesis, and their production in S . scabiei is in turn...

Rotihibins A and B are plant growth inhibitors acting on the TORK pathway. We report the isolation and characterization of new sequence analogues of rotihibin from Streptomyces scabies , a major cause of common scab in potato and other tuber and root vegetables.

Bioactive natural products are typically secreted by the producer strain. Besides that, this allows the targeting of competitors, also filling a protective role, reducing the chance of self-killing. Surprisingly, DNA-degrading and membrane damaging prodiginines (PdGs) are only produced intracellularly, and are required for the onset of the second r...

In the plant pathogen Streptomyces scabies, the gene bglC encodes a GH1 family cellobiose beta-glucosidase that is both required for primary metabolism and for inducing virulence of the bacterium. Deletion of bglC (strain ΔbglC) surprisingly resulted in the augmentation of the global beta-glucosidase activity of S. scabies. This paradoxical phenoty...

Strain prioritization for drug discovery aims at excluding redundant strains of a collection in order to limit the repetitive identification of the same molecules. In this work, we wanted to estimate what can be unexploited in terms of the amount, diversity, and novelty of compounds if the search is focused on only one single representative strain...

Access to whole-genome sequences has exposed the general incidence of the so-called cryptic biosynthetic gene clusters (BGCs), thereby renewing their interest for natural product discovery. As a consequence, genome mining is the often first approach implemented to assess the potential of a microorganism for producing novel bioactive metabolites. By...

Biosynthetic gene clusters (BGCs) are organized groups of genes involved in the production of specialized metabolites. Typically, one BGC is responsible for the production of one or several similar compounds with bioactivities that usually only vary in terms of strength and/or specificity. Here we show that the previously described ferroverdins and...

Actinobacteria are prolific producers of antitumor antibiotics with antiproliferative activity, but why these bacteria synthetize metabolites with this bioactivity has so far remained a mystery. In this work we raised the hypothesis that under certain circumstances, production of antiproliferative agents could be part of a genetically programmed de...

In the model species Streptomyces coelicolor A3(2), the uptake of chitin-degradation byproducts, mainly N,N′-diacetylchitobiose ([GlcNAc] 2) and N-acetylglucosamine (GlcNAc), is performed by the ATP-binding cassette (ABC) transporter DasABC-MsiK and the sugar-phosphotransferase system (PTS), respectively. Studies on the S. coelicolor chromosome hav...

Common scab disease on root and tuber plants is caused by Streptomyces scabies and related species which use the cellulose synthase inhibitor thaxtomin A as the main phytotoxin. Thaxtomin production is primarily triggered by the import of cello-oligosaccharides. Once inside the cell, the fate of the cello-oligosaccharides is dichotomized into i) fu...

Streptomyces lunaelactis MM109 T is a ferroverdin A (anticholesterol) producer isolated from cave moonmilk deposits. The complete genome sequence of MM109 T was obtained by combining Oxford Nanopore MinION and Illumina HiSeq and MiSeq technologies, revealing an 8.4-Mb linear chromosome and two plasmids, pSLUN1 (127,264 bp, linear) and pSLUN2 (46,82...

Streptomyces and few other Actinobacteria naturally produce compounds currently used in chemotherapy for being cytotoxic against various types of tumor cells by damaging the DNA structure and/or inhibiting DNA functions. DNA-damaging antitumor antibiotics belong to different classes of natural compounds that are structurally unrelated such as anthr...

Cave moonmilk deposits host an abundant and diverse actinobacterial population that has a great potential for producing novel natural bioactive compounds. In our previous attempt to isolate culturable moonmilk-dwelling Actinobacteria, only Streptomyces species were recovered, whereas a metagenetic study of the same deposits revealed a complex actin...

Moonmilk are cave carbonate deposits that host a rich microbiome, including antibiotic-producing Actinobacteria, making these speleothems appealing for bioprospecting. Here, we investigated the taxonomic profile of the actinobacterial community of three moonmilk deposits of the cave “Grotte des Collemboles” via high-throughput sequencing of 16S rRN...

Moonmilk are cave carbonate deposits that host a rich microbiome including antibiotic-producing Actinobacteria making these speleothems appealing for bioprospecting. Here we investigated the taxonomic profile of the actinobacterial community of three moonmilk deposits of the cave “Grotte des Collemboles” via high-throughput sequencing of 16S rRNA a...

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...

The World Health Organization (WHO) describes antibiotic resistance as "one of the biggest threats to global health, food security, and development today", as the number of multi- and pan-resistant bacteria is rising dangerously. Acquired resistance phenomena also impair antifungals, antivirals, anti-cancer drug therapy, while herbicide resistance...

Common scab disease on root and tuber plants is caused by Streptomyces scabies and related species which use the cellulose synthase inhibitor thaxtomin A as main phytotoxin. Thaxtomin production is primarily triggered by the import of cello-oligosaccharides. Once inside the cell, the fate of the cello-oligosaccharides is dichotomized into i) fuelin...

The explosive increase in genome sequencing and the advances in bioinformatic tools have revolutionized the rationale for natural product discovery from actinomycetes. In particular, this has revealed that actinomycete genomes contain numerous orphan gene clusters that have the potential to specify many yet unknown bioactive specialized metabolites...

The explosive increase in genome sequencing and the advances in bioinformatic tools have revolutionized the rationale for natural product discovery from actinomycetes. In particular, this has revealed that actinomycete genomes contain numerous orphan gene clusters that have the potential to specify many yet unknown bioactive specialized metabolites...

Moonmilk is a karstic speleothem mainly composed of fine calcium carbonate crystals (CaCO3) with different textures ranging from pasty to hard, in which the contribution of biotic rock-building processes is presumed to involve indigenous microorganisms. The real microbial input in the genesis of moonmilk is difficult to assess leading to controvers...

Moonmilk is a karstic speleothem mainly composed of fine calcium carbonate crystals (CaCO 3 ) with different textures ranging from pasty to hard, in which the contribution of biotic rock-building processes is presumed to involve indigenous microorganisms. The real bacterial input in the genesis of moonmilk is difficult to assess leading to controve...

The acquisition of genetic material conferring the arsenal necessary for host virulence is a prerequisite on the path to becoming a plant pathogen. More subtle mutations are also required for the perception of cues signifying the presence of the target host and optimal conditions for colonization. The decision to activate the pathogenic lifestyle i...

The acquisition of genetic material conferring the arsenal necessary for host virulence is a prerequisite on the path to become a plant pathogen. More subtle mutations are also required for perception of cues witnessing the presence of the target host and optimal conditions for colonization. The decision to activate the pathogenic lifestyle is not...

In the era that huge numbers of microbial genomes are being released in the databases, it becomes increasingly important to rapidly mine genes as well as predict the regulatory networks that control their expression. To this end, we have developed an improved and online version of the PREDetector software aimed at identifying putative transcription...

Moonmilk speleothems of limestone caves host a rich microbiome, among which Actinobacteria represent one of the most abundant phyla. Ancient medical texts reported that moonmilk had therapeutical properties, thereby suggesting that its filamentous endemic actinobacterial population might be a source of natural products useful in human treatment. In...

Streptomyces scabies is an economically important plant pathogen well-known for damaging root and tuber crops by causing scab lesions. Thaxtomin A is the main causative agent responsible for the pathogenicity of S. scabies and cello-oligosaccharides are environmental triggers that induce the production of this phytotoxin. How cello-oligosaccharides...

Actinobacteria are producers of a plethora of natural products of agricultural, biotechnological and clinical importance. In an era where mankind has to deal with rapidly spreading antimicrobial resistance, streptomycetes are of particular importance as producers of half of all antibiotics used in the clinic. Genome sequencing efforts revealed that...

Dormancy is a state of growth cessation that allows bacteria to escape the host defense system and antibiotic challenge. Understanding the mechanisms that control dormancy is of key importance for the treatment of latent infections, such as those from Mycobacterium tuberculosis . In mycobacteria, dormancy is controlled by the response regulator Dev...

Bacterial resistance to antibiotics is on the rise and a return to the ‘pre-antibiotic’ era has become a frightening possibility. Various factors are responsible for this situation: the overuse of antibiotics in human medicine and animal husbandry, insufficient public funding for research into fundamental bacteriology including resistance mechanism...

The GntR-family transcription regulator, DasR, was previously identified as pleiotropic, controlling the primary amino sugar N-acetylglucosamine (GlcNAc) and chitin metabolism in Saccharopolyspora erythraea and Streptomyces coelicolor. Due to the remarkable regulatory impact of DasR on antibiotic production and development in the model strain of S....

Due to the necessity of iron for housekeeping functions, nutrition, morphogenesis, and secondary metabolite production, siderophore piracy could be a key strategy in soil and substrate colonisation by microorganisms. Here we report that mutants of bacterium Streptomyces coelicolor unable to produce desferrioxamine siderophores could recover growth...

Streptomycetes produce a wealth of natural products, including over half of all known antibiotics. It was previously demonstrated that N-acetylglucosamine and secondary metabolism are closely entwined in streptomycetes. Here we show that DNA recognition by the N-acetylglucosamine-responsive regulator DasR is growth-phase dependent, and that DasR ca...

Unlabelled: A relatively small number of species in the large genus Streptomyces are pathogenic; the best characterized of these is Streptomyces scabies. The pathogenicity of S. scabies strains is dependent on the production of the nitrated diketopiperazine thaxtomin A, which is a potent plant cellulose synthesis inhibitor. Much is known about the...

The in silico prediction of cis-acting elements in a genome is an efficient way to quickly obtain an overview of the biological processes controlled by a trans-acting factor, and connections between regulatory networks. Several regulon prediction web tools are available, designed to identify DNA motifs predicted to be bound by transcription factors...

A novel actinobacterium, designated MM109T, was isolated from a moonmilk deposit collected from the cave 'Grotte des Collemboles' located in Comblain-au-Pont, Belgium. Based on a polyphasic taxonomic approach comprising chemo-taxonomic, phylogenetic, morphological, and physio-logical characterization, the isolate has been affiliated to the genus St...

Chitin degradation and subsequent N-acetylglucosamine (GlcNAc) catabolism is thought to be a common trait of a large majority of actinomycetes. Aminosugars utilization had been poorly investigated outside the model strain Streptomyces coelicolor A3(2), and we examined here the genetic setting of the erythromycin producer Saccharopolyspora erythraea...

Nitrogen source sensing, uptake, and assimilation are central for growth and development of microorganisms which requires the participation of a global control of nitrogen metabolism-associated genes at the transcriptional level. In soil-dwelling antibiotic-producing actinomycetes, this role is played by GlnR, an OmpR family regulator. In this work...

Streptomyces coelicolor is an important model organism for developmental studies of filamentous GC-rich actinobacteria. The genetic characterization of mutants of S. coelicolor blocked at the vegetative mycelium stage, the so-called bald (bld) mutants that are unable to erect spore-forming aerial hyphae, has opened the way to discovering the molecu...

Prodigiosin-like pigments or prodiginines (PdGs) are promising drugs owing to their reported antitumor, antibiotic, and immunosuppressive activities. These natural compounds are produced by several bacteria, including Streptomyces coelicolor and Serratia marcescens as most commonly studied models. The bright red color of these tripyrrole pigments m...

Iron is one of the most abundant elements on earth but is found in poorly soluble forms hardly accessible to microorganisms. To subsist, they have developed iron-chelating molecules called siderophores that capture this element in the environment and the resulting complexes are internalized by specific uptake systems. While biosynthesis of sideroph...

N-acetylglucosamine (GlcNAc), the monomer of chitin and constituent of bacterial peptidoglycan, is a preferred carbon and nitrogen source for streptomycetes. Recent studies have revealed new functions of GlcNAc in nutrient signaling of bacteria. Exposure to GlcNAc activates development and antibiotic production of Streptomyces coelicolor under poor...

Filamentous microorganisms of the bacterial genus Streptomyces have a complex life cycle that includes physiological and morphological differentiations. It is now fairly well accepted that lysis of Streptomyces vegetative mycelium induced by programmed cell death (PCD) provides the required nutritive sources for the bacterium to erect spore-forming...

A copper-sensitive operon repressor protein (CsoR) has been identified in Streptomyces lividans (CsoR(Sl)) and found to regulate copper homeostasis with attomolar affinity for Cu(I). Solution studies reveal apo- and Cu(I)-CsoR(Sl) to be a tetramer assembly, and a 1.7-Å resolution crystal structure of apo-CsoR(Sl) reveals that a significant conforma...

N-Acetylglucosamine, the monomer of chitin, is a favored carbon and nitrogen source for streptomycetes. Its intracellular catabolism requires the combined actions of the N-acetylglucosamine-6-phosphate (GlcNAc-6P) deacetylase NagA and the glucosamine-6-phosphate (GlcN-6P) deaminase/isomerase NagB. GlcNAc acts as a signaling molecule in the DasR-med...