Ero1-Pdi1 module-catalysed dimerization of a nucleotide sugar transporter, FonNst2, regulates virulence of Fusarium oxysporum on watermelon.

Fusarium oxysporum f. sp. niveum (Fon) is a soil-borne fungus causing vascular Fusarium wilt on watermelon; however, the molecular network regulating Fon virulence remains to be elucidated. Here, we report the function and mechanism of nucleotide sugar transporters (Nsts) in Fon. Fon genome harbours nine FonNst genes with distinct functions in vegetative growth, asexual production, cell wall stress response and virulence. FonNst2 and FonNst3 are required for full virulence of Fon on watermelon and FonNst2 is mainly involved in fungal colonization of the plant tissues. FonNst2 and FonNst3 form homo- or hetero-dimers but function independently in Fon virulence. FonNst2, which has UDP-galactose transporter activity in yeast, interacts with FonEro1 and FonPdi1, both of which are required for full virulence of Fon. FonNst2, FonPdi1 and FonEro1 target to endoplasmic reticulum (ER) and are essential for ER homeostasis and function. FonEro1-FonPdi1 module catalyses the dimerization of FonNst2, which is critical for Fon virulence. Undimerized FonNst2 is unstable and degraded via ER-associated protein degradation in vivo. These data demonstrate that FonEro1-FonPdi1 module-catalysed dimerization of FonNst2 is critical for Fon virulence on watermelon and provide new insights into the regulation of virulence in plant fungal pathogens via disulfide bond formation of key pathogenicity factors.