Unveiling molecular mechanisms of strobilurin resistance in the cacao pathogen Moniliophthora perniciosa

Strobilurin fungicides inhibit mitochondrial respiration, leading to ATP depletion and oxidative stress. Although widely used in agriculture, these chemicals are ineffective against the cacao pathogen Moniliophthora perniciosa. Here, we show that M. perniciosa tolerates high concentrations of the commercial strobilurin azoxystrobin in vitro. Transcriptomic analysis revealed that short-term exposure triggers upregulation of genes related to catabolic pathways, including the glyoxylate cycle and fatty acid degradation, alongside repression of genes involved in anabolic processes, such as cell division and ribosome biogenesis. Simultaneously, genes associated with cellular detoxification and oxidative stress responses were strongly induced. These alterations suggest that M. perniciosa remodels its metabolism to counteract fungicide toxicity. Remarkably, long-term exposure to azoxystrobin led to the emergence of a resistant mutant harboring mutations in two putative growth and transcriptional regulators. This work provides new insights into the molecular basis of strobilurin resistance and informs strategies for more effective fungicide deployment in agriculture.