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

Jing Wang,Zhonghua Ma,Gabriele Berg,Chaoyun Xu,Jinrong Xu,Tomislav Cernava,Yun Chen,Yunrong Chai,Qiming Sun

doi:10.1186/s40168-021-01077-y

Abstract

BackgroundMicrobiome 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.ResultsIn 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 26S 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.ConclusionsAutophagy 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.3Zu6EQMv78RbwrwJHF2G1TVideo abstract

Highlights

A balanced microbiome is important for human, plant, and environmental health, while diseases are often associated with microbial dysbiosis [1]
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

Summary

Introduction

A balanced microbiome is important for human, plant, and environmental health, while diseases are often associated with microbial dysbiosis [1]. Bacteria and fungi often show negative co-occurrence trends in such communities, which indicates that the former suppress the latter [11]. This is important in connection with recent evidence that the microbiota of a healthy host can naturally harbor various pathogenic fungi, which can result in disease outbreaks when they are enriched [12]. MTORC1 (mammalian target of rapamycin complex 1) represses autophagy through the regulation of the ULK1 (a homolog of yeast Atg1)-Atg13-FIP200 protein complex formation by directly phosphorylating ULK1 at Ser758 under nutrient-rich conditions [23, 24]. Both are ubiquitous members of the healthy wheat microbiota; under dysbiosis, the fungus causes devastating diseases

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