title: Bioactivities by a crude extract from the Greenlandic Pseudomonas sp. In5 involves the nonribosomal peptides, nunamycin and nunapeptin.
abstract: Background. Bioactive microbial metabolites provide a successful source of novel compounds with pharmaceutical potentials. The bacterium Pseudomonas sp. In5 is a biocontrol strain isolated from a plant disease suppressive soil in Greenland, which produces two antimicrobial nonribosomal peptides (NRPs), nunapeptin and nunamycin. Methods. In this study, we used in vitro antimicrobial and anticancer bioassays to evaluate the potential bioactivities of both a crude extract derived from Pseudomonas sp. In5 and NRPs purified from the crude extract. Results. We verified that the crude extract derived from Pseudomonas sp. In5 showed suppressive activity against the basidiomycete Rhizoctonia solani by inducing a mitochondrial stress-response. Furthermore, we confirmed suppressive activity against the oomycete Pythium aphanidermatum by the Pseudomonas sp. In5 crude extract, and that the purified nunamycin and nunapeptin displayed distinct antimicrobial activities. In addition to the antimicrobial activity, we found that treatment of the cancer cell lines, Jurkat T-cells, Granta cells, and melanoma cells, with the Pseudomonas sp. In5 crude extract increased staining with the apoptotic marker Annexin V while no staining of healthy normal cells, i.e., naïve or activated CD4 T-cells, was observed. Treatment with either of the NRPs alone did not increase Annexin V staining of the Jurkat T-cells, despite individually showing robust antimicrobial activity, whereas an anticancer activity was detected when nunamycin and nunapeptin were used in combination. Discussion. Our results suggest that the bioactivity of a crude extract derived from Pseudomonas sp. In5 involves the presence of both nunamycin and nunapeptin and highlight the possibility of synergy between multiple microbial metabolites.
authors.affiliation: Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark.
authors.forename: Charlotte F
authors.initials: CF
authors.lastname: Michelsen
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, CA, United States.
authors.forename: Helle
authors.initials: H
authors.lastname: Jensen
authors.affiliation: Departments of Bioengineering and Therapeutic Sciences, School of Pharmacy, University of California, San Francisco, CA, United States.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Venditto
authors.affiliation: Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Rosanna C
authors.initials: RC
authors.lastname: Hennessy
authors.affiliation: Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Stougaard
keywords: Anticancer; Antimicrobial; Crude extract; Nonribosomal peptides; Pseudomonas