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A broad-spectrum anti-fungal effector dictates bacterial-fungal interkingdom interactions

Summary

Scientists discovered that a common soil bacterium called Acidovorax citrulli has a sophisticated weapon to fight dangerous fungi. This bacterium uses a needle-like structure to inject a toxic protein called TseN directly into fungal cells, where it damages the fungal DNA and causes death. This new discovery is particularly exciting because it works against drug-resistant fungi like Candida auris that are increasingly hard to treat. Tests in mice confirmed that this bacterial attack significantly reduces fungal infections on skin.

Background

Bacteria and fungi frequently co-inhabit complex environments where competition for resources shapes community composition. While bacterial inhibition of fungi through diffusible metabolites is well-documented, direct delivery of protein effectors into fungal cells remains rare and poorly understood. The type VI secretion system (T6SS) has emerged as a potential weapon for interkingdom antagonism.

Objective

To identify and characterize anti-fungal effectors delivered by the T6SS of Acidovorax citrulli and elucidate the mechanisms of bacterial-fungal competition. The study focuses on understanding how bacterial effectors can directly target fungal cells and suppress pathogenic fungi including drug-resistant strains.

Results

TseN was identified as the primary antifungal T6SS effector possessing a unique C-terminal DNase domain and nuclear localization signal. The effector exhibits broad-spectrum activity against Candida auris, Cryptococcus neoformans, Candida albicans, and other fungi. In vivo experiments demonstrated significant reduction of C. auris fungal burden in mouse skin infections, and TseN enhanced azole efficacy against drug-resistant C. albicans.

Conclusion

TseN represents a novel class of DNase effector that directly targets fungal cell nuclei to suppress growth. The discovery of this broad-spectrum anti-fungal mechanism and the prevalence of TseN homologs across bacterial species suggests potential therapeutic applications for combating fungal infections in clinical and environmental settings.
  • Published in:PLoS Pathogens,
  • Study Type:Original Research,
  • Source: 10.1371/journal.ppat.1013598, PMID: 41144565
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