Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans
Abstract 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...
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Nature Portfolio
2025-06-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-60234-1 |
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| author | Lena Peters Moritz Drechsler Michael A. Herrera Jing Liu Barbara Pees Johanna Jarstorff Anna Czerwinski Francesca Lubbock Georgia Angelidou Liesa Salzer Karlis Arturs Moors Nicole Paczia Yi-Ming Shi Hinrich Schulenburg Christoph Kaleta Michael Witting Manuel Liebeke Dominic J. Campopiano Helge B. Bode Katja Dierking |
| author_facet | Lena Peters Moritz Drechsler Michael A. Herrera Jing Liu Barbara Pees Johanna Jarstorff Anna Czerwinski Francesca Lubbock Georgia Angelidou Liesa Salzer Karlis Arturs Moors Nicole Paczia Yi-Ming Shi Hinrich Schulenburg Christoph Kaleta Michael Witting Manuel Liebeke Dominic J. Campopiano Helge B. Bode Katja Dierking |
| author_sort | Lena Peters |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-1ef9873a9d054d6e998769af28a79bae |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-1ef9873a9d054d6e998769af28a79bae2025-08-20T03:10:34ZengNature PortfolioNature Communications2041-17232025-06-0116111810.1038/s41467-025-60234-1Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegansLena Peters0Moritz Drechsler1Michael A. Herrera2Jing Liu3Barbara Pees4Johanna Jarstorff5Anna Czerwinski6Francesca Lubbock7Georgia Angelidou8Liesa Salzer9Karlis Arturs Moors10Nicole Paczia11Yi-Ming Shi12Hinrich Schulenburg13Christoph Kaleta14Michael Witting15Manuel Liebeke16Dominic J. Campopiano17Helge B. Bode18Katja Dierking19Department of Evolutionary Ecology and Genetics, Zoological Institute, Kiel UniversityDepartment of Natural Products in Organismic Interactions, Max-Planck-Institute for Terrestrial MicrobiologySchool of Chemistry, The University of EdinburghDepartment of Natural Products in Organismic Interactions, Max-Planck-Institute for Terrestrial MicrobiologyDepartment of Evolutionary Ecology and Genetics, Zoological Institute, Kiel UniversityDepartment of Evolutionary Ecology and Genetics, Zoological Institute, Kiel UniversityDepartment of Evolutionary Ecology and Genetics, Zoological Institute, Kiel UniversitySchool of Chemistry, The University of EdinburghCore Facility for Metabolomics and Small Molecule Mass Spectrometry, Max Planck Institute for Terrestrial MicrobiologyResearch Unit Analytical BioGeoChemistry, Helmholtz Zentrum MünchenResearch Group Medical Systems Biology, Institute for Experimental Medicine, Kiel UniversityCore Facility for Metabolomics and Small Molecule Mass Spectrometry, Max Planck Institute for Terrestrial MicrobiologyDepartment of Natural Products in Organismic Interactions, Max-Planck-Institute for Terrestrial MicrobiologyDepartment of Evolutionary Ecology and Genetics, Zoological Institute, Kiel UniversityResearch Group Medical Systems Biology, Institute for Experimental Medicine, Kiel UniversityMetabolomics and Proteomics Core, Helmholtz Zentrum MünchenDepartment of Metabolomics, Institute for Human Nutrition and Food Science, Kiel UniversitySchool of Chemistry, The University of EdinburghDepartment of Natural Products in Organismic Interactions, Max-Planck-Institute for Terrestrial MicrobiologyDepartment of Evolutionary Ecology and Genetics, Zoological Institute, Kiel UniversityAbstract 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.https://doi.org/10.1038/s41467-025-60234-1 |
| spellingShingle | Lena Peters Moritz Drechsler Michael A. Herrera Jing Liu Barbara Pees Johanna Jarstorff Anna Czerwinski Francesca Lubbock Georgia Angelidou Liesa Salzer Karlis Arturs Moors Nicole Paczia Yi-Ming Shi Hinrich Schulenburg Christoph Kaleta Michael Witting Manuel Liebeke Dominic J. Campopiano Helge B. Bode Katja Dierking Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans Nature Communications |
| title | Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans |
| title_full | Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans |
| title_fullStr | Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans |
| title_full_unstemmed | Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans |
| title_short | Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans |
| title_sort | polyketide synthase derived sphingolipids mediate microbiota protection against a bacterial pathogen in c elegans |
| url | https://doi.org/10.1038/s41467-025-60234-1 |
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