Post-translational regulation of autophagy is involved in intra-microbiome suppression of fungal pathogens

Background: Microbiome interactions are important determinants for ecosystem functioning, stability, and health. In previous studies, it was often observed that bacteria suppress potentially pathogenic fungal species that are part of the same plant microbiota; however, the underlying microbe-microbe interplay remains mostly elusive. Here, we explored antagonistic interactions of the fungus Fusarium graminearum and bacterium Streptomyces hygroscopicus at the molecular level. Both are ubiquitous members of the healthy wheat microbiota; under dysbiosis, the fungus causes devastating diseases. Results: In co-cultures, we found that Streptomyces alters the fungal acetylome leading to substantial induction of fungal autophagy. The bacterium secrets rapamycin to inactivate the target of rapamycin (TOR), which subsequently promotes the degradation of the fungal histone acetyltransferase Gcn5 through the 265 proteasome. Gcn5 negatively regulates fungal autophagy by acetylating the autophagy-related protein Atg8 at the lysine site K13 and blocking cellular relocalization of Atg8. Thus, degradation of Gcn5 triggered by rapamycin was found to reduce Atg8 acetylation, resulting in autophagy induction in F. graminearum. Conclusions: Autophagy homeostasis plays an essential role in fungal growth and competition, as well as for virulence. Our work reveals a novel post-translational regulation of autophagy initiated by a bacterial antibiotic. Rapamycin was shown to be a powerful modulator of bacteria-fungi interactions with potential importance in explaining microbial homeostasis in healthy plant microbiomes. The autophagic process provides novel possibilities and targets to biologically control pathogens.

Automated summary

In this study, antagonistic interactions between the fungus Fusarium graminearum and bacterium Streptomyces hygroscopicus were explored at the molecular level. Streptomyces altered the fungal acetylome, leading to induction of fungal autophagy, with the mechanism involving rapamycin secretion inhibiting TOR and degrading Gcn5, ultimately reducing Atg8 acetylation and promoting autophagy in F. graminearum. This novel post-translational regulation of autophagy initiated by a bacterial antibiotic provides insights into microbial homeostasis in healthy plant microbiomes and offers new possibilities for controlling pathogens.