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The broad-spectrum antibiotic, zeamine, kills the nematode worm Caenorhabditis elegans.

ABSTRACT: Soil bacteria can be prolific producers of secondary metabolites and other biologically active compounds of economic and clinical importance. These natural products are often synthesized by large multi-enzyme complexes such as polyketide synthases (PKSs) or non-ribosomal peptide synthases (NRPSs). The plant-associated Gram-negative bacterium, Serratia plymuthica A153, produces several secondary metabolites and is capable of killing the nematode worm Caenorhabditis elegans; a commonly used model for the study of bacterial virulence. In this study, we show that disruption of the hybrid PKS/NRPS zeamine (zmn) gene cluster results in the attenuation of "fast-killing" of C. elegans, indicating that zeamine has nematicidal activity. C. elegans also exhibits age-dependent susceptibility to zeamine, with younger worms being most sensitive to the bioactive molecule. The zmn gene cluster is widely distributed within Serratia and phytopathogenic Dickeya species and investigation of strains harboring the zmn gene cluster showed that several of them are highly virulent in C. elegans. Zeamine was described previously as a phytotoxin and broad-spectrum antibacterial compound. In addition to its nematicidal properties, we show here that zeamine can also kill Saccharomyces cerevisiae and Schizosaccharomyces pombe. The expression of the zmn gene cluster and regulation of zeamine production were also investigated. Transcription of the cluster was growth phase-dependent, and was modulated by the post-transcriptional RNA chaperone, Hfq. The results of this study show that zeamine is a highly toxic molecule with little, or no, apparent host specificity in very diverse biological systems. In its current form, zeamine(s) may be useful as a lead compound suitable for chemical modification and structure-activity assays. However, because of widespread non-selective toxicity in multiple bioassays, unmodified zeamine(s) is unlikely to be suitable as a therapeutic antibiotic.

SUBMITTER: Hellberg JE

PROVIDER: S-EPMC4341552 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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The broad-spectrum antibiotic, zeamine, kills the nematode worm Caenorhabditis elegans.

Hellberg Josephine E E U JE Matilla Miguel A MA Salmond George P C GP

Frontiers in microbiology 20150226

Soil bacteria can be prolific producers of secondary metabolites and other biologically active compounds of economic and clinical importance. These natural products are often synthesized by large multi-enzyme complexes such as polyketide synthases (PKSs) or non-ribosomal peptide synthases (NRPSs). The plant-associated Gram-negative bacterium, Serratia plymuthica A153, produces several secondary metabolites and is capable of killing the nematode worm Caenorhabditis elegans; a commonly used model ...[more]

PMID: 25767467

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Project description:Caenorhabditis (C.) elegans has become a popular toxicological and biological test organism in the last two decades. Furthermore, the role of C. elegans as an alternative for replacing or reducing animal experiments is continuously discussed and investigated. In the current study, we investigated whether C. elegans survival assays can help in determining differences in the virulence of Salmonella enterica strains and to what extent C. elegans assays could replace animal experiments for this purpose. We focused on three currently discussed examples where we compared the longevity of C. elegans when fed (i) with S. enterica serovar Enteritidis vaccination or wild-type strains, (ii) with lipopolysaccharide (LPS) deficient rough or LPS forming smooth S. enterica serovar Enteritidis, and (iii) with an S. enterica subsp. diarizonae strain in the presence or absence of the typical pSASd plasmid encoding a bundle of putative virulence factors. We found that the C. elegans survival assay could indicate differences in the longevity of C. elegans when fed with the compared strain pairs to a certain extent. Putatively higher virulent S. enterica strains reduced the lifespan of C. elegans to a greater extent than putatively less virulent strains. The C. elegans survival assay is an effective and relatively easy method for classifying the virulence of different bacterial isolates in vivo, but it has some limitations. The assay cannot replace animal experiments designed to determine differences in the virulence of Salmonella enterica strains. Instead, we recommend using the described method for pre-screening bacterial strains of interest to select the most promising candidates for further animal experiments. The C. elegans assay possesses the potential to reduce the number of animal experiments. Further development of the C. elegans assay in conjunction with omics technologies, such as transcriptomics, could refine results relating to the estimation of the virulent potential of test organisms.

Dataset Information

The broad-spectrum antibiotic, zeamine, kills the nematode worm Caenorhabditis elegans.

Publications

The broad-spectrum antibiotic, zeamine, kills the nematode worm Caenorhabditis elegans.

Similar Datasets

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