Abstract

Carbon catabolite repression (CCR) acts as a switch, reprogramming nutrient utilization in fungal pathogens during the growth-to-colonization transition. However, whether this regulatory system can be exploited by other microbes remains unknown. Here, we demonstrate that Pseudomonas CXZ-8 attenuates the virulence of Fusarium graminearum by hijacking fungal CCR. CXZ-8 disrupts the infection-induced nuclear-to-cytoplasmic relocalization of the CCR master regulator FgCreA, thereby suppressing FCO1 expression, which is crucial for both host cell wall degradation and nutrient acquisition. This interference also benefits the bacterium by preventing the accumulation of host-derived indole derivatives and fungal mycotoxins that threaten its survival. Notably, approximately 20% of field-isolated bacteria exhibit similar FgCreA-stabilizing activity. Furthermore, we assembled a microbial consortium enriched for CCR-targeting bacteria, which conferred broad-spectrum disease resistance in field trials. These findings reveal a novel mode of interkingdom interference and establish CCR as a conserved microbial vulnerability, with implications for sustainable, microbiome-based crop protection.