Understanding the genetic pathways that regulate how pathogenic fungi respond to their environment is paramount to developing effective mitigation strategies against disease. Carbon catabolite repression (CCR) is a global regulatory mechanism found in a wide range of microbial organisms that ensures the preferential utilization of glucose over less favourable carbon sources, but little is known about the components of CCR in filamentous fungi. Here we report three new mediators of CCR in the devastating rice blast fungus Magnaporthe oryzae : the sugar sensor Tps1, the Nmr1-3 inhibitor proteins, and the multidrug and toxin extrusion (MATE)–family pump, Mdt1. Using simple plate tests coupled with transcriptional analysis, we show that Tps1, in response to glucose-6-phosphate sensing, triggers CCR via the inactivation of Nmr1-3. In addition, by dissecting the CCR pathway using Agrobacterium tumefaciens -mediated mutagenesis, we also show that Mdt1 is an additional and previously unknown regulator of glucose metabolism. Mdt1 regulates glucose assimilation downstream of Tps1 and is necessary for nutrient utilization, sporulation, and pathogenicity. This is the first functional characterization of a MATE–family protein in filamentous fungi and the first description of a MATE protein in genetic regulation or plant pathogenicity. Perturbing CCR in Δ tps1 and MDT1 disruption strains thus results in physiological defects that impact pathogenesis, possibly through the early expression of cell wall–degrading enzymes. Taken together, the importance of discovering three new regulators of carbon metabolism lies in understanding how M. oryzae and other pathogenic fungi respond to nutrient availability and control development during infection. Author Summary To succeed as pathogens, fungi such as the rice blast fungus M. oryzae must adapt their metabolism to nutrient availability within the host, but little is known about the genetic regulatory mechanisms involved. M. oryzae destroys enough rice to feed 60 million people annually, and understanding how the infection process is controlled would afford new targets for anti-rice blast strategies and shed light on regulatory pathways common to other pathogenic fungi. Here we use M. oryzae to identify and describe three new regulators of global carbon metabolism in filamentous fungi: the sugar-sensor Tps1; the transcription factor inhibitor proteins Nmr1-3; and a transmembrane efflux pump Mdt1 (the first pump of its type to be described in pathogenic filamentous fungi), which is essential for sporulation and pathogenicity. Tps1, Nmr1-3, and Mdt1 are shown to control the fungal response to glucose availability, and perturbation of this regulatory pathway abolishes disease. This work gives fresh insights into nutrient adaptation and the control of fungal development during infection and is thus applicable to a wide range of fungal pathogens.
【초록키워드】 Pathogenesis, Genetic, Infection, metabolism, Regulatory, Protein, inactivation, pathway, understanding, target, Pathogens, repression, pathogenicity, inhibitor, fungi, disease, expression, mechanism, fungal, Glucose, Mutagenesis, Analysis, regulate, strain, Trigger, Perturbation, microbial, physiological, triggers, transcription factor, mediators, sugar, Agrobacterium tumefaciens, catabolite repression, glucose metabolism, genetic regulation, cell wall, Regulation, principle, Author, infection process, components, Glucose-6-phosphate, transmembrane, pathogenic, organism, component, carbon, fungal pathogens, filamentous fungi, sporulation, Carbon catabolite repression, carbon metabolism, cell wall–degrading enzymes, M. oryzae, MATE protein, MATE–family protein, Mdt1, Nmr1, Nmr1-3, Nmr1-3 inhibitor proteins, nutrient availability, regulatory pathways, Tps1, regulatory pathway, downstream, pump, BLAST, Host, effective, transcriptional, found, shown, described, identify, involved, addition, functional, less, respond, CCR, Catabolite, Rice, Agrobacterium tumefacien, abolishes disease, Magnaporthe, carbon sources, 【제목키워드】 catabolite repression, glucose metabolism,