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

do Prado, P. F. V.; Mendes, C. V. C.; Pires, B. A.; Fiorin, G. L.; Mieczkowski, P.; Pereira, G. A. G.; Teixeira, P. J. P. L.; Thomazella, D. P. d. T.

doi:10.1101/2024.11.14.623591

bioRxiv · 10.1101/2024.11.14.623591

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

do Prado, P. F. V.·Mendes, C. V. C.·Pires, B. A.·Fiorin, G. L.·Mieczkowski, P.·Pereira, G. A. G.·Teixeira, P. J. P. L.·Thomazella, D. P. d. T.

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Abstract

Witches broom disease (WBD) is a major constraint for cacao production in the Americas. The severe socioeconomic impact of WBD encouraged the evaluation of different control strategies, including the use of strobilurin fungicides. These molecules inhibit mitochondrial respiration, thus impairing ATP generation and leading to oxidative stress. These chemicals, however, have proven ineffective against the WBD pathogen Moniliophthora perniciosa. Here, we demonstrate that M. perniciosa tolerates high concentrations of strobilurins under in vitro conditions and highlight a set of molecular alterations that correlate with strobilurin tolerance in this fungus. Short-term exposure of M. perniciosa to the commercial strobilurin azoxystrobin led to the up-regulation of genes encoding enzymes of the glyoxylate cycle, gluconeogenesis, and fatty acid and amino acid catabolism, indicating that the fungal metabolism is remodeled to compensate for reduced ATP production. Furthermore, cell division, ribosome biogenesis, and sterol metabolism were repressed, which agrees with the impaired mycelial growth on azoxystrobin. Genes associated with cellular detoxification and response to oxidative stress (e.g., cytochrome P450s, membrane transporters and glutathione s-transferases) were strongly induced by the drug and represent potential strategies used by the pathogen to mitigate the toxic effects of the fungicide. Remarkably, exposure of M. perniciosa to azoxystrobin resulted in the spontaneous generation of a mutant with increased resistance to strobilurin. Comparative genomics and transcriptomics revealed alterations that may explain the resistance phenotype, including a large deletion in a putative transcriptional regulator and significant changes in the mutant transcriptome. Overall, this work provides important advances towards a comprehensive understanding of the molecular basis of strobilurin resistance in a tropical fungal pathogen. This is a fundamental step to efficiently employ these fungicides in agriculture and to prevent the emergence of strobilurin resistance.

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do Prado, P. F. V., Mendes, C. V. C., Pires, B. A., Fiorin, G. L., Mieczkowski, P., Pereira, G. A. G., Teixeira, P. J. P. L., Thomazella, D. P. d. T.. 2024-11-14. Unveiling novel mechanisms of strobilurin resistance in the cacao pathogen Moniliophthora perniciosa. https://doi.org/10.1101/2024.11.14.623591

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