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Background <p>Fungal–prokaryotic interactions are widespread in natural and host-associated habitats. These interactions are believed to play crucial roles in ecosystem functioning and health. However, the cell–cell interaction mechanisms between these two types of microorganisms remain largely unknown.</p> Results <p>We demonstrate that fungi <i>Saccharomyces cerevisiae</i> and <i>Cryptococcus neoformans</i> secrete 4-hydroxy-5-methyl-3(2<i>H</i>)-furanone (MHF), which chemoattracts <i>Pseudomonas aeruginosa</i> via the dCache_1-type ligand-binding domains (LBDs) of the chemoreceptors PctA and TlpQ. We also solved high-resolution structures of PctA-LBD and TlpQ-LBD in complex with MHF. Bioinformatic analyses suggest that the MHF synthase Cff1p is widespread among fungi, and functionally distinct dCache_1-containing transmembrane receptors capable of sensing MHF are prevalent across diverse bacteria and archaea. Functional assays confirm MHF binding enhances enzymatic activities of representative dCache_1-type LBD-containing receptors. Finally, communication network analysis suggests that MHF-mediated fungal–prokaryotic interactions are widespread between members of the fungal phyla Ascomycota and Basidiomycota and the bacterial phyla Pseudomonadota and Bacillota.</p> Conclusions <p>These findings identify MHF as a broadly utilised fungal signal mediating extensive interkingdom communications between fungi and prokaryotes, highlighting its potential role in shaping microbial community dynamics.</p>

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4-hydroxy-5-methyl-3(2H)-furanone mediates widespread interkingdom communications between fungi and prokaryotes

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月15日

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  • Xinyu Qian,
  • Yan-Bo Zhao,
  • Heng Zhang,
  • Wenguang Yang,
  • Kai Sun,
  • Songying Ouyang,
  • Xihui Shen,
  • Lei Zhang

摘要

Background

Fungal–prokaryotic interactions are widespread in natural and host-associated habitats. These interactions are believed to play crucial roles in ecosystem functioning and health. However, the cell–cell interaction mechanisms between these two types of microorganisms remain largely unknown.

Results

We demonstrate that fungi Saccharomyces cerevisiae and Cryptococcus neoformans secrete 4-hydroxy-5-methyl-3(2H)-furanone (MHF), which chemoattracts Pseudomonas aeruginosa via the dCache_1-type ligand-binding domains (LBDs) of the chemoreceptors PctA and TlpQ. We also solved high-resolution structures of PctA-LBD and TlpQ-LBD in complex with MHF. Bioinformatic analyses suggest that the MHF synthase Cff1p is widespread among fungi, and functionally distinct dCache_1-containing transmembrane receptors capable of sensing MHF are prevalent across diverse bacteria and archaea. Functional assays confirm MHF binding enhances enzymatic activities of representative dCache_1-type LBD-containing receptors. Finally, communication network analysis suggests that MHF-mediated fungal–prokaryotic interactions are widespread between members of the fungal phyla Ascomycota and Basidiomycota and the bacterial phyla Pseudomonadota and Bacillota.

Conclusions

These findings identify MHF as a broadly utilised fungal signal mediating extensive interkingdom communications between fungi and prokaryotes, highlighting its potential role in shaping microbial community dynamics.