Reference - Detail
| RRC ID | 88114 |
|---|---|
| Author | Peters L, Drechsler M, Herrera MA, Liu J, Pees B, Jarstorff J, Czerwinski A, Lubbock F, Angelidou G, Salzer L, Moors KA, Paczia N, Shi YM, Schulenburg H, Kaleta C, Witting M, Liebeke M, Campopiano DJ, Bode HB, Dierking K. |
| Title | Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans. |
| Journal | Nat Commun |
| 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. |
| Volume | 16(1) |
| Pages | 5151 |
| Published | 2025-6-3 |
| DOI | 10.1038/s41467-025-60234-1 |
| PII | 10.1038/s41467-025-60234-1 |
| PMID | 40461452 |
| PMC | PMC12134224 |
| MeSH | Animals Bacillus thuringiensis / pathogenicity Caenorhabditis elegans* / immunology Caenorhabditis elegans* / metabolism Caenorhabditis elegans* / microbiology Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Gastrointestinal Microbiome* Host-Pathogen Interactions Polyketide Synthases* / genetics Polyketide Synthases* / metabolism Pseudomonas fluorescens* / genetics Pseudomonas fluorescens* / metabolism Serine C-Palmitoyltransferase / genetics Serine C-Palmitoyltransferase / metabolism Sphingolipids* / metabolism |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 40 |
| Altmetric score changes over past 6months | 0.7 |
| Resource | |
| C.elegans | tm495 tm609 tm3036 |