AUTHOR=Hellberg Josephine E., Matilla Miguel A., Salmond George P.

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

JOURNAL=Frontiers in Microbiology

VOLUME=6

YEAR=2015

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2015.00137

DOI=10.3389/fmicb.2015.00137

ISSN=1664-302X

ABSTRACT=<p>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, <italic>Serratia plymuthica</italic> A153, produces several secondary metabolites and is capable of killing the nematode worm <italic>Caenorhabditis elegans</italic>; a commonly used model for the study of bacterial virulence. In this study, we show that disruption of the hybrid PKS/NRPS zeamine (<italic>zmn</italic>) gene cluster results in the attenuation of “fast-killing” of <italic>C. elegans</italic>, indicating that zeamine has nematicidal activity. <italic>C. elegans</italic> also exhibits age-dependent susceptibility to zeamine, with younger worms being most sensitive to the bioactive molecule. The <italic>zmn</italic> gene cluster is widely distributed within <italic>Serratia</italic> and phytopathogenic <italic>Dickeya</italic> species and investigation of strains harboring the <italic>zmn</italic> gene cluster showed that several of them are highly virulent in <italic>C. elegans</italic>. 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 <italic>Saccharomyces cerevisiae</italic> and <italic>Schizosaccharomyces pombe</italic>. The expression of the <italic>zmn</italic> 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.</p>