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<p>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 <i>Caenorhabditis elegans</i> and its microbiota isolate <i>Pseudomonas fluorescens</i> MYb115 that is known to protect against <i>Bacillus thuringiensis</i> (Bt) infection. We find that MYb115-mediated protection depends on sphingolipids (SLs) that are derived from an iterative type I polyketide synthase (PKS) cluster <i>Pf</i>SgaAB, 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 <i>Pf</i>SgaB 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 <i>C. elegans</i> 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.</p>

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Polyketide synthase-derived sphingolipids mediate microbiota protection against a bacterial pathogen in C. elegans

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年6月3日

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  • 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

摘要

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.