title: A Phenotypic and Genotypic Analysis of the Antimicrobial Potential of CultivableStreptomycesIsolated from Cave Moonmilk Deposits.
abstract: 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 this work, a screening approach was undertaken in order to isolate cultivable Actinobacteria from moonmilk of the Grotte des Collemboles in Belgium, to evaluate their taxonomic profile, and to assess their potential in biosynthesis of antimicrobials. Phylogenetic analysis revealed that all 78 isolates were exclusively affiliated to the genusStreptomycesand clustered into 31 distinct phylotypes displaying various pigmentation patterns and morphological features. Phylotype representatives were tested for antibacterial and antifungal activities and their genomes were mined for secondary metabolite biosynthetic genes coding for non-ribosomal peptide synthetases (NRPSs), and polyketide synthases (PKS). The moonmilkStreptomycescollection was found to display strong inhibitory activities against a wide range of reference organisms, as 94, 71, and 94% of the isolates inhibited or impaired the growth of Gram-positive, Gram-negative bacteria, and fungi, respectively. Interestingly, 90% of the cave strains induced strong growth suppression against the multi-drug resistantRasamsonia argillacea, a causative agent of invasive mycosis in cystic fibrosis and chronic granulomatous diseases. No correlation was observed between the global antimicrobial activity of an individual strain and the number of NRPS and PKS genes predicted in its genome, suggesting that approaches for awakening cryptic metabolites biosynthesis should be applied to isolates with no antimicrobial phenotype. Overall, our work supports the common belief that moonmilk might effectively treat various infectious diseases thanks to the presence of a highly diverse population of prolific antimicrobial producingStreptomyces, and thus may indeed constitute a promising reservoir of potentially novel active natural compounds.
authors.affiliation: InBioS - Centre for Protein Engineering, Institut de Chimie B6a, University of Liège Liège, Belgium.
authors.forename: Marta
authors.initials: M
authors.lastname: Maciejewska
authors.affiliation: InBioS - Centre for Protein Engineering, Institut de Chimie B6a, University of Liège Liège, Belgium.
authors.forename: Delphine
authors.initials: D
authors.lastname: Adam
authors.affiliation: InBioS - Centre for Protein Engineering, Institut de Chimie B6a, University of Liège Liège, Belgium.
authors.forename: Loïc
authors.initials: L
authors.lastname: Martinet
authors.affiliation: InBioS - Centre for Protein Engineering, Institut de Chimie B6a, University of Liège Liège, Belgium.
authors.forename: Aymeric
authors.initials: A
authors.lastname: Naômé
authors.affiliation: Environmental Research and Innovation Department, Luxembourg Institute of Science and Technology Belvaux, Luxembourg.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Całusińska
authors.affiliation: Environmental Research and Innovation Department, Luxembourg Institute of Science and Technology Belvaux, Luxembourg.
authors.forename: Philippe
authors.initials: P
authors.lastname: Delfosse
authors.affiliation: InBioS - Plant and Microbial Ecology, Botany B22, University of Liège Liège, Belgium.
authors.forename: Monique
authors.initials: M
authors.lastname: Carnol
authors.affiliation: Department of Biology, University of Akron, Akron OH, USA.
authors.forename: Hazel A
authors.initials: HA
authors.lastname: Barton
authors.affiliation: Department of Clinical Microbiology, University Hospital of Liège Liège, Belgium.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Hayette
authors.affiliation: MolSys Research Unit, Mass Spectrometry Laboratory, University of Liège Liège, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Smargiasso
authors.affiliation: MolSys Research Unit, Mass Spectrometry Laboratory, University of Liège Liège, Belgium.
authors.forename: Edwin
authors.initials: E
authors.lastname: De Pauw
authors.affiliation: InBioS - Functional Genomics and Plant Molecular Imaging, University of LiègeLiège, Belgium; PhytoSYSTEMS, University of LiègeLiège, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Hanikenne
authors.affiliation: PhytoSYSTEMS, University of LiègeLiège, Belgium; InBioS - Eukaryotic Phylogenomics, University of LiègeLiège, Belgium.
authors.forename: Denis
authors.initials: D
authors.lastname: Baurain
authors.affiliation: InBioS - Centre for Protein Engineering, Institut de Chimie B6a, University of Liège Liège, Belgium.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Rigali
keywords: MLSA phylogeny; cryptic antibiotics; genome mining; geomicrobiology; secondary metabolism