Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans
Protection against pathogens is a major function of the gut microbiota. Although bacterial natural products have emerged as crucial components of host-microbiota interactions, their exact role in microbiota-mediated protection is largely unexplored. We addressed this knowledge gap with the nematode Caenorhabditis elegans and its microbiota isolate Pseudomonas fluorescens MYb115 that is known to protect against Bacillus thuringiensis (Bt) infection. We find that MYb115-mediated protection depends on sphingolipids (SLs) that are derived from an iterative type I polyketide synthase (PKS) cluster PfSgaAB, thereby revealing a non-canonical pathway for the production of bacterial SLs as secondary metabolites. SL production is common in eukaryotes but was thought to be limited to a few bacterial phyla that encode the serine palmitoyltransferase (SPT) enzyme, which catalyses the initial step in SL synthesis. We demonstrate that PfSgaB encodes a pyridoxal 5'-phosphate-dependent alpha-oxoamine synthase with SPT activity, and find homologous putative PKS clusters present across host-associated bacteria that are so far unknown SL producers. Moreover, we provide evidence that MYb115-derived SLs affect C. elegans defence against Bt infection by altering SL metabolism in the nematode host. This work establishes SLs as structural outputs of bacterial PKS and highlights the role of microbiota-derived SLs in host protection against pathogens.
Authors
- Lena Peters (ORCID: https://orcid.org/0000-0003-1007-3409)
- Katja Dierking (ORCID: https://orcid.org/0000-0002-5129-346X)
- Georgia Angelidou (ORCID: https://orcid.org/0000-0002-1238-0122)
- Yi‐Ming Shi (ORCID: https://orcid.org/0000-0001-6933-4971)
- Hinrich Schulenburg (ORCID: https://orcid.org/0000-0002-1413-913X)
- Karlis Arturs Moors (ORCID: https://orcid.org/0000-0001-6529-2970)
- Michael A. Witting (ORCID: https://orcid.org/0000-0002-1462-4426)
- Helge B. Bode (ORCID: https://orcid.org/0000-0001-6048-5909)
- Barbara Pees (ORCID: https://orcid.org/0009-0004-4791-4683)
- Manuel Liebeke (ORCID: https://orcid.org/0000-0002-2339-1409)
- Anna Czerwinski (ORCID: https://orcid.org/0000-0002-7468-1262)
- Michael A. Herrera (ORCID: https://orcid.org/0000-0001-8693-8910)
- Liesa Salzer (ORCID: https://orcid.org/0000-0003-0761-0656)
- Christoph Kaleta (ORCID: https://orcid.org/0000-0001-8004-9514)
- Dominic J. Campopiano (ORCID: https://orcid.org/0000-0001-8573-6735)
- Moritz Drechsler (ORCID: https://orcid.org/0009-0009-2444-2237)
- Nicole Paczia (ORCID: https://orcid.org/0000-0003-3859-8186)
- Jing Liu (ORCID: https://orcid.org/0000-0002-3588-2969)
- Johanna Jarstorff
- Francesca Lubbock
Institutions
- Goethe University Frankfurt (DE)
- Chinese Academy of Sciences (CN)
- Senckenberg - Leibniz Institution for Biodiversity and Earth System Research (DE)
- Helmholtz Zentrum München (DE)
- Hochschule für Angewandte Wissenschaften Kiel (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Max Planck Institute for Marine Microbiology (DE)
- Loewe Center for Synthetic Microbiology (DE)
- Shenzhen Institutes of Advanced Technology (CN)
- Max Planck Institute for Evolutionary Biology (DE)
- Max Planck Institute for Terrestrial Microbiology (DE)
- Phillips University (US)
- Technical University of Munich (DE)
- University of Edinburgh (GB)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-06-03
- DOI
- https://doi.org/10.1038/s41467-025-60234-1
- Citations
- 5
- Primary Topic
- Genetics, Aging, and Longevity in Model Organisms
- Type
- article
- Field-Weighted Citation Impact
- 4.77
Funders
- University of Minnesota
- Deutsche Forschungsgemeinschaft
- National Institutes of Health
- Directorate for Biological Sciences
- Biotechnology and Biological Sciences Research Council
- Helmholtz Zentrum München