Acetate provokes mitochondrial stress and cell death in Ustilago maydis

Abstract

The fungal pathogen Ustilago maydis causes disease on maize by mating to establish an infectious filamentous cell type that invades the host and induces tumours. We previously found that β-oxidation mutants were defective in virulence and did not grow on acetate. Here, we demonstrate that acetate inhibits filamentation during mating and in response to oleic acid. We therefore examined the influence of different carbon sources by comparing the transcriptomes of cells grown on acetate, oleic acid or glucose, with expression changes for the fungus during tumour formation in planta. Guided by the transcriptional profiling, we found that acetate negatively influenced resistance to stress, promoted the formation of reactive oxygen species, triggered cell death in stationary phase and impaired virulence on maize. We also found that acetate induced mitochondrial stress by interfering with mitochondrial functions. Notably, the disruption of oxygen perception or inhibition of the electron transport chain also influenced filamentation and mating. Finally, we made use of the connections between acetate and β-oxidation to test metabolic inhibitors for an influence on growth and virulence. These experiments identified diclofenac as a potential inhibitor of virulence. Overall, these findings support the possibility of targeting mitochondrial metabolic functions to control fungal pathogens.

Deletion of ptn1, a PTEN/TEP1 Orthologue, in Ustilago maydis Reduces Pathogenicity and Teliospore Development

“…The fusion of haploid cells during mating leads to the differentiation of U. maydis into subsequent filamentous dikaryon [20]. Also, environmental conditions such as acidic pH, lipids, and low ammonium conditions can trigger the filamentous response in U. maydis [37,38,39], while acetate inhibits filamentation, due to mating or to exposure to oleic acid [40]. Hence, a qRT-PCR analysis was conducted for several genes involved in the mating pathway, e.g., mfa2 , encoding a2 pheromone precursor, pra2 , encoding pheromone receptor, and prf1 , encoding a transcription factor [41].…”

Transcripts and tumors: regulatory and metabolic programming during biotrophic phytopathogenesis

“…Other carbon sources such as organic acids (fatty acids or carboxylic acids) may also contribute to the carbon supply of the pathogen at early time points of infection on the cuticle and at a late stage during spore formation 36 . Monocarboxylic acids are a carbon source for U. maydis in vitro but can have detrimental effects on fungal longevity and reactive oxygen species resistance 37 . Ustilago is known to inhibit the transition to C4 metabolism that is dependent on the dicarboxylate malate for transport between cells.…”

Revealing the high variability on nonconserved core and mobile elements of Austropuccinia psidii and other rust mitochondrial genomes

“…The methylation of the mitochondrial genome is an epigenetic mechanism affecting the adaptation and pathogenicity of Candida albicans [32]. Furthermore, mitochondrial metabolic functions are targets for pathogen control [33,34].…”