Bacterial endosymbionts protect beneficial soil fungus from nematode attack Hannah Büttner †,1 , Sarah P. Niehs †,1 , Koen Vandelannoote 2 , Zoltán Cseresnyés 3 , Benjamin Dose 1 , Ingrid Richter 1 , Ruman Gerst 3,4 , Marc Thilo Figge 3,4 , Timothy P. Stinear 2 , Sacha J. Pidot* ,2 , Christian Hertweck* ,1,4 1 Leibniz Institute for Natural Product Research and Infection Biology, Hans Knöll Institute, Germany, 2 Doherty Institute, Australia, 3 Applied Systems Biology Research Group, Leibniz Institute for Natural Product Research and Infection Biology, Germany, 4 University Jena, Germany, † These authors contributed equally to this paper Healthy soil is indispensable for agriculture, important for clean water and air, and the nutritional source for plants and animals. It is also a complex and competitive environment with concurrent soil-dwelling microorganisms, animals and plants, all requiring nutrients, minerals and carbon sources. Especially saprophytes and decomposer, like fungi of the genus Mortierella , play pivotal roles in carbon cycling, xenobiont degradation and plant growth promotion. Despite their important role in healthy soils, the knowledge on their protective traits is limited. We have found that Mortierella verticillata NRRL 6337 shields itself from nematodal micropredators with the help of a toxin-producing endobacterial symbiont. We provide evidence that the highly cytotoxic macrolactones (CJ-12,950 and CJ-13,357, syn. necroxime C and D), which were believed to be fungal metabolites, are in fact produced by a previously overlooked bacterial endosymbiont, Candidatus Mycoavidus necroximicus. Using the model organism Caenorhabditis elegans and the fungivorous nematode Aphelenchus avenae , we probed the anthelmintic activity of the necroximes and demonstrated the effective host protection in cocultures of nematodes with symbiotic and chemically complemented aposymbiotic fungal strains. This study reveals an important function for endofungal bacteria as producer of protecting agents and opens the possibility for the development of new biocontrol agents. References 1. H. Büttner, S. P. Niehs et al., Proc. Natl. Acad. Sci. U.S.A. 118, e2110669118 (2021) 2. K. A. Dekker et al., J. Antibiot. 51, 14-20 (1998)
3. S. P. Niehs et al., Angew. Chem. Int. Ed. 59, 7766-7771 (2020) 4. R. Ueoka et al., Angew. Chem. Int. Ed. 59, 7761-7765 (2020) 5. D. L. Galinis et al., J. Org. Chem. 62, 8968-8969 (1997)
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