Antinematode activity of violacein and the role of the insulin/IGF-1 pathway in controlling violacein sensitivity in Caenorhabditis elegans

Francesco Ballestriero*, Malak Daim, Anahit Penesyan, Jadranka Nappi, David Schleheck, Paolo Bazzicalupo, Elia Di Schiavi, Suhelen Egan

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    21 Citations (Scopus)
    52 Downloads (Pure)

    Abstract

    The purple pigment violacein is well known for its numerous biological activities including antibacterial, antiviral, antiprotozoan, and antitumor effects. In the current study we identify violacein as the antinematode agent produced by the marine bacterium Microbulbifer sp. D250, thereby extending the target range of this small molecule. Heterologous expression of the violacein biosynthetic pathway in E. coli and experiments using pure violacein demonstrated that this secondary metabolite facilitates bacterial accumulation in the nematode intestine, which is accompanied by tissue damage and apoptosis. Nematodes such as Caenorhabditis elegans utilise a well-defined innate immune system to defend against pathogens. Using C. elegans as a model we demonstrate the DAF-2/DAF-16 insulin/IGF-1 signalling (IIS) component of the innate immune pathway modulates sensitivity to violacein-mediated killing. Further analysis shows that resistance to violacein can occur due to a loss of DAF-2 function and/or an increased function of DAF-16 controlled genes involved in antimicrobial production (spp-1) and detoxification (sod-3). These data suggest that violacein is a novel candidate antinematode agent and that the IIS pathway is also involved in the defence against metabolites from non-pathogenic bacteria.

    Original languageEnglish
    Article numbere109201
    Pages (from-to)1-12
    Number of pages12
    JournalPLoS ONE
    Volume9
    Issue number10
    DOIs
    Publication statusPublished - 8 Oct 2014

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