Uncertainty surrounding the mechanism and safety of the post-harvest fungicide fludioxonil

Abstract

Fludioxonil is a phenylpyrrole pesticide that is applied to fruit and vegetable crops post-harvest to minimize losses to mold, both during transport and at point of sale. Its effectiveness is reflected in the dramatic increase in its production/usage since its introduction in 1994, an increase that has peaked in recent years as it became licenced for use abroad. Recently, doubts as to the nature of its mechanism of action have been raised. Given that the pesticide has long been known to induce stress intermediates in target and non-target organisms alike, the lack of a firmly established mechanism might be cause for concern. Troubling reports further delineate a capacity to disrupt hepatic, endocrine and neurological systems, indicating that fludioxonil may represent a health threat to consumers. In the absence of a clear, safe mechanism of action, fludioxonil should be re-evaluated for its potential to impact human health.

Keywords: Aldehydic; Oxidative; Pesticide; Phenylpyrrole; Pyrrolnitrin; Toxicity.

Figure 1.. Theoretical mechanism of fludioxonil action.

We postulate that instead of acting directly upon a prototypical hybrid histidine kinase (HHK), fludioxonil instead creates a stress state in affected cells. Stress intermediates derived from this state are then detected via their modification of sentinel cysteines present in the HHK, inducing a structural shift that favors the phosphatase activity of the HHK over the kinase activity. Dephosphorylation of Ypd1 directly activates the HOG1 cascade, interfering with cell cycle and glycerol production pathways and swiftly rendering the cell non-viable. This model is based in part on published data (Lawry et al., 2017).