Principles of carbon catabolite repression in the rice blast fungus: Tps1, Nmr1-3, and a MATE-family pump regulate glucose metabolism during infection.
Principles of carbon catabolite repression in the rice blast fungus: Tps1, Nmr1-3, and a MATE-family pump regulate glucose metabolism during infection.
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DOI：
10.1371/journal.pgen.1002673
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Wilson RA
中科院分区：
文献类型：
--
作者：
Fernandez J;Wright JD;Hartline D;Quispe CF;Madayiputhiya N;Wilson RA
了解调节致病真菌如何对其环境作出反应的遗传途径对于制定有效的疾病缓解策略至关重要。碳分解代谢物阻遏（CCR）是一种广泛存在于微生物中的全局性调控机制，可确保对葡萄糖的优先利用，但目前对丝状真菌中CCR的组成成分知之甚少。在这里，我们报告了三个新的介质CCR在毁灭性的稻瘟病菌：糖传感器Tps 1，Nmr 1 -3抑制剂蛋白，和多药和毒素挤出（MATE）-家庭泵，Mdt 1。使用简单的平板测试加上转录分析，我们表明，Tps 1，在响应葡萄糖-6-磷酸传感，触发CCR通过Nmr 1 -3的失活。此外，通过使用根癌农杆菌介导的诱变解剖CCR途径，我们还表明，Mdt 1是一个额外的和以前未知的葡萄糖代谢调节。Mdt 1调节Tps 1下游的葡萄糖同化，并且是营养利用、孢子形成和致病性所必需的。这是丝状真菌中MATE家族蛋白的第一个功能特征，也是MATE蛋白在遗传调控或植物致病性中的第一个描述。因此，在Δ tps 1和MDT 1破坏菌株中干扰CCR导致影响发病机制的生理缺陷，可能通过细胞壁降解酶的早期表达。总之，发现三种新的碳代谢调节因子的重要性在于了解M。真菌和其他病原真菌在感染过程中对营养物质的可用性和控制发展作出反应。为了成功地作为病原体，真菌如稻瘟病菌M。寄生虫必须使它们的代谢适应宿主内的营养供应，但对所涉及的遗传调控机制知之甚少。M.稻瘟病每年摧毁的水稻足以养活6000万人，了解感染过程是如何控制的将为抗稻瘟病策略提供新的目标，并揭示其他病原真菌常见的调控途径。这里我们使用M。本研究旨在确定和描述丝状真菌中三种新的全球碳代谢调节因子：糖传感器Tps 1;转录因子抑制蛋白Nmr 1 -3;和跨膜外排泵Mdt 1（致病性丝状真菌中描述的第一种泵），这对孢子形成和致病性至关重要。Tps 1，Nmr 1 -3，和Mdt 1被证明控制真菌对葡萄糖的利用率的反应，这种调节途径的干扰消除疾病。这项工作提供了新的见解营养适应和感染过程中真菌发育的控制，因此适用于广泛的真菌病原体。
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 Δtps1 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. 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.
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DOI：
10.1080/21501203.2011.563431
发表时间：
2011-01-01
期刊：
Mycology - An International Journal on Fungal Biology
影响因子：
--
作者：
Fernandez, J.;Wilson, R. A.
通讯作者：
Wilson, R. A.
DOI：
10.1111/j.1432-1033.1975.tb03958.x
发表时间：
1975-01-01
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
BAILEY, C;ARST, HN
通讯作者：
ARST, HN
影响因子：
3.2
作者：
Andrianopoulos, A;Kourambas, S;Hynes, MJ
通讯作者：
Hynes, MJ
影响因子：
5.3
作者：
DOWZER, CEA;KELLY, JM
通讯作者：
KELLY, JM
影响因子：
56.9
作者：
Alonso, JM;Stepanova, AN;Ecker, JR
通讯作者：
Ecker, JR