Functional mechanistic diversity of the NUDIX effectors in fungal pathogens

Abstract NUcleoside Diphosphate-linked to moiety X (NUDIX) hydrolases are ubiquitous enzymes that maintain metabolic homeostasis by hydrolyzing potentially toxic nucleoside diphosphates. In plants and other eukaryotes, inositol pyrophosphates (PP-InsPs) act as central signaling molecules, linking cellular phosphate status to gene expression via SPX-domain receptors. A recent study (McCombe et al., Science 387:955–962, 2025) showed that several plant pathogenic fungi secrete NUDIX effector proteins that hydrolyze PP-InsPs and manipulate host phosphate signaling. In the blast fungus Magnaporthe oryzae , a cytoplasmic NUDIX effector (MoNUDIX) hydrolyzes PP-InsPs, triggers a phosphate starvation response and suppresses immunity in rice, thereby facilitating disease progression. In contrast, the lentil anthracnose pathogen Colletotrichum lentis secretes CtNUDIX into the apoplast, where it disrupts PP-InsP-dependent endocytic machinery and elicits a hypersensitive cell death response. Collectively, these findings demonstrate how NUDIX effectors exemplify mechanistic diversification within a single effector family: manipulating phosphate signaling promotes biotrophic colonization, whereas disrupting host membrane integrity induces a switch to necrotrophy.