title: Antinematode activity of Violacein and the role of the insulin/IGF-1 pathway in controlling violacein sensitivity in Caenorhabditis elegans.
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.
authors.affiliation: School of Biotechnology and Biomolecular Sciences and Centre for Marine Bio-Innovation, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Francesco
authors.initials: F
authors.lastname: Ballestriero
authors.affiliation: School of Biotechnology and Biomolecular Sciences and Centre for Marine Bio-Innovation, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Malak
authors.initials: M
authors.lastname: Daim
authors.affiliation: Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, New South Wales, Australia.
authors.forename: Anahit
authors.initials: A
authors.lastname: Penesyan
authors.affiliation: School of Biotechnology and Biomolecular Sciences and Centre for Marine Bio-Innovation, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Jadranka
authors.initials: J
authors.lastname: Nappi
authors.affiliation: Biology Department, University of Konstanz, Konstanz, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Schleheck
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso", National Research Council, Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Bazzicalupo
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso", National Research Council, Naples, Italy.
authors.forename: Elia
authors.initials: E
authors.lastname: Di Schiavi
authors.affiliation: School of Biotechnology and Biomolecular Sciences and Centre for Marine Bio-Innovation, University of New South Wales, Sydney, New South Wales, Australia.
authors.forename: Suhelen
authors.initials: S
authors.lastname: Egan
mesh_terms: D034241:Alteromonadaceae / Q000378:metabolism*; D000818:Animals; D000969:Antinematodal Agents / Q000378:metabolism / Q000494:pharmacology*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D004251:DNA Transposable Elements / Q000235:genetics; D007211:Indoles / Q000378:metabolism / Q000494:pharmacology*; D007328:Insulin / Q000235:genetics / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism*
chemical_list: D000969:Antinematodal Agents; D004251:DNA Transposable Elements; D007211:Indoles; D007328:Insulin; D007334:Insulin-Like Growth Factor I; C063155:violacein