Peters, L.* ; Drechsler, M.* ; Herrera, M.A.* ; Liu, J.* ; Pees, B.* ; Jarstorff, J.* ; Czerwinski, A.* ; Lubbock, F.* ; Angelidou, G.* ; Salzer, L. ; Moors, K.A.* ; Paczia, N.* ; Shi, Y.M.* ; Schulenburg, H.* ; Kaleta, C.* ; Witting, M. ; Liebeke, M.* ; Campopiano, D.J.* ; Bode, H.B.* ; Dierking, K.*
Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans.
Nat. Commun. 16:5151 (2025)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
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Keywords
Serine Palmitoyltransferase; 3-ketosphinganine Reductase; Biosynthesis; Gene; Metabolism; Pathways; Activation; Expression; Proteins
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Language
english
Publication Year
2025
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0
HGF-reported in Year
2025
ISSN (print) / ISBN
2041-1723
e-ISSN
2041-1723
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Volume: 16,
Issue: 1,
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Article Number: 5151
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Nature Publishing Group
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London
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Peer reviewed
POF-Topic(s)
30202 - Environmental Health
30505 - New Technologies for Biomedical Discoveries
Research field(s)
Environmental Sciences
Enabling and Novel Technologies
PSP Element(s)
G-504800-001
A-630710-001
Grants
Projekt DEAL
German Science Foundation DFG
Max-Planck Society
ERC
NIH Office of Research Infrastructure Programs
Biotechnology and Biological Sciences Research Council (BBSRC)
German Science Foundation DFG (Collaborative Research Center CRC1182 Origin and Function of Metaorganisms)
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Erfassungsdatum
2025-06-05