Lipophagy acts as a nutritional adaptation mechanism for the filamentous entomopathogenic fungus Beauveria bassiana to colonize within the hosts

Abstract

Introduction

Metabolic adaptation to various nutrients is crucial for the pathogenic growth and virulence of filamentous fungal pathogens. Despite its importance, the mechanisms underlying fungal adaptation to nutrient shifts, especially at the subcellular level, remain incompletely understood.

Objectives

Our study aims to investigate the mechanisms involved in metabolic adaptation in filamentous fungi.

Methods

The filamentous entomopathogenic fungus Beauveria bassiana was used as a representative of filamentous fungi. Gene functional analyses were characterized via gene disruption and complementation. Vacuolar targeting of lipid droplets were determined with transmission electron microscopy and fluorescence microscopy. Protein interaction was determined with yeast-two hybridization and co-immunoprecipitation methods.

Results

The filamentous entomopathogenic fungus Beauveria bassiana was found to initiate autophagy, and further lipophagy, when transitioning from utilizing fatty acids to carbohydrates, while also proliferating in the host hemocoel. The disruption of three critical autophagy-related genes (ATG), specifically BbATG1, BbATG8, and BbATG11, hindered the vacuolar targeting of lipid droplets (LD) and worsened the impaired growth and dimorphism in fatty acid medium subjected to cell-wall perturbance stress. Notably, BbSun4, a protein containing a SUN4 domain, was required for lipophagy, as it tagged the lipid droplets. BbMcp, which features a methyl-accepting chemotaxis-like domain, engaged directly with both BbAtg8 and BbSun4, thereby enhancing the interaction between these proteins. It is important to note that BbMcp solely facilitated lipophagy during nutrient shifts rather than during starvation stress. The loss of lipophagy proved detrimental to the integrity of the fungal cytomembrane, growth, and overall development, ultimately leading to a marked reduction in virulence.

Conclusion

Lipophagy is a molecular pathway that consists of a selective autophagy receptor, a bridging factor, and Atg8, which is essential for fungal metabolic adaptation during colonizing within the host niches. This study deepens our understanding of the molecular mechanism underling the fungus-host interaction and vacuolar targeting pathways in selective autophagy.