title: Eliciting antibiotics active against the ESKAPE pathogens in a collection of actinomycetes isolated from mountain soils.
abstract: The rapid emergence of multidrug-resistant (MDR) bacterial pathogens poses a major threat for human health. In recent years, genome sequencing has unveiled many poorly expressed antibiotic clusters in actinomycetes. Here, we report a well-defined ecological collection of >800 actinomycetes obtained from sites in the Himalaya and Qinling mountains, and we used these in a concept study to see how efficiently antibiotics can be elicited against MDR pathogens isolated recently from the clinic. Using 40 different growth conditions, 96 actinomycetes were identified - predominantly Streptomyces - that produced antibiotics with efficacy against the MDR clinical isolates referred to as ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and/or Enterobacter cloacae. Antimicrobial activities that fluctuated strongly with growth conditions were correlated with specific compounds, including borrelidin, resistomycin, carbomethoxy-phenazine, and 6,7,8- and 5,6,8-trimethoxy-3-methylisocoumarin, of which the latter was not described previously. Our work provided insights into the potential of actinomycetes as producers of drugs with efficacy against clinical isolates that have emerged recently and also underlined the importance of targeting a specific pathogen.
authors.affiliation: Molecular Biotechnology, Institute of Biology, Molecular Biotechnology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Jasper
authors.initials: J
authors.lastname: Swierstra
authors.affiliation: Molecular Biotechnology, Institute of Biology, Molecular Biotechnology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Changsheng
authors.initials: C
authors.lastname: Wu
authors.affiliation: Molecular Biotechnology, Institute of Biology, Molecular Biotechnology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Girard
authors.affiliation: Natural Products Laboratory, Institute of Biology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Young Hae
authors.initials: YH
authors.lastname: Choi
authors.affiliation: Department of Medical Microbiology and Infectious Diseases, Erasmus Medical Centre, 's Gravendijkwal 230, 3015 CE Rotterdam, The Netherlands.
authors.forename: Willem
authors.initials: W
authors.lastname: van Wamel
authors.affiliation: Molecular Biotechnology, Institute of Biology, Molecular Biotechnology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Sandiford
authors.affiliation: Molecular Biotechnology, Institute of Biology, Molecular Biotechnology, Leiden University, Sylviusweg 72, 2333 BE Leiden, The Netherlands.
authors.forename: Gilles P
authors.initials: GP
authors.lastname: van Wezel
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects; D039903:Actinobacteria / Q000145:classification / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D001424:Bacterial Infections / Q000382:microbiology; D002681:China; D024901:Drug Resistance, Multiple, Bacterial; D016972:Enterobacter cloacae / Q000187:drug effects; D016984:Enterococcus faecium / Q000187:drug effects; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012988:Soil Microbiology; D013211:Staphylococcus aureus / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents