Bioactivities by a crude extract from the GreenlandicPseudomonassp. In5 involves the nonribosomal peptides, nunamycin and nunapeptin

Author:

Michelsen Charlotte F.1,Jensen Helle2,Venditto Vincent J.3,Hennessy Rosanna C.4,Stougaard Peter4

Affiliation:

1. Department of Systems Biology, Technical University of Denmark, Kgs. Lyngby, Denmark

2. Department of Microbiology and Immunology, University of California, San Francisco, CA, United States

3. Departments of Bioengineering and Therapeutic Sciences, School of Pharmacy, University of California, San Francisco, CA, United States

4. Department of Plant and Environmental Sciences, University of Copenhagen, Frederiksberg C, Denmark

Abstract

Background.Bioactive microbial metabolites provide a successful source of novel compounds with pharmaceutical potentials. The bacteriumPseudomonassp. 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 usedin vitroantimicrobial and anticancer bioassays to evaluate the potential bioactivities of both a crude extract derived fromPseudomonassp. In5 and NRPs purified from the crude extract.Results.We verified that the crude extract derived fromPseudomonassp. In5 showed suppressive activity against the basidiomyceteRhizoctonia solaniby inducing a mitochondrial stress-response. Furthermore, we confirmed suppressive activity against the oomycetePythium aphanidermatumby thePseudomonassp. 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 thePseudomonassp. 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 fromPseudomonassp. In5 involves the presence of both nunamycin and nunapeptin and highlight the possibility of synergy between multiple microbial metabolites.

Funder

Commission for Scientific Research in Greenland

Publisher

PeerJ

Subject

General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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