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.
Highlights
Parasitic nematodes are an important group of human, animal and plant pathogens representing a major threat to public health, and to livestock and agricultural industries around the globe [1]
We further show that the expression of enzymes that synthesize violacein in E. coli facilitates bacterial accumulation in the host intestine and induces apoptosis in the nematode
Sequencing of the four non-active mutants revealed that in all cases transposons had inserted in open reading frames with high sequence identity to the vioABCDE gene cluster of C. violaceum, which has previously been shown to be involved in the synthesis of violacein [37] (Table 3)
Summary
Parasitic nematodes are an important group of human, animal and plant pathogens representing a major threat to public health, and to livestock and agricultural industries around the globe [1]. Heavy reliance on the few available chemotherapeutic agents has resulted in the development of nematode resistance and little progress has been made in the search for new treatments [2,3]. There is an urgent requirement for the discovery of new antinematode compounds that can be developed into chemotherapeutic drugs. The nematode C. elegans is a powerful model organism used broadly across the fields of cellular biology, developmental biology and neurobiology, and more recently as a model organism for the study of host-microbial interactions with a focus on pathogenesis and drug discovery [4,5]. In a recent functional screen of genomic libraries of marine bacteria, a number of fosmid clones expressing high toxicity towards C. elegans were identified [6]. Genetic analysis of the insert revealed that the clone 20G8 contained genes encoding for the synthesis of the indole-antibiotic violacein (vioA-E) [6], suggesting that this metabolite is responsible for its toxic phenotype
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
