Niche-specific regulation of central metabolic pathways in a fungal pathogen.
Niche-specific regulation of central metabolic pathways in a fungal pathogen.
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DOI：
10.1111/j.1462-5822.2005.00676.x
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发表时间：
2006-06
影响因子：
3.4
通讯作者：
Brown AJ
中科院分区：
文献类型：
--
作者：
Barelle CJ;Priest CL;Maccallum DM;Gow NA;Odds FC;Brown AJ
为了建立感染，病原体白色念珠菌必须吸收碳并在其哺乳动物宿主中生长。这种真菌通过糖酵解途径同化六碳化合物，通过乙醛酸循环和异源生殖同化二碳化合物。我们解决了一个矛盾的作用，这些中央代谢途径在C。白色念珠菌发病机制：乙醛酸循环显然是毒力所必需的，尽管乙醛酸循环基因被血流中存在的浓度的葡萄糖抑制。利用GFP融合蛋白，我们证实了C.白色念珠菌的基因被生理相关浓度的葡萄糖抑制，并且显示这些基因在感染小鼠肾脏的大多数真菌细胞中是无活性的。然而，这些途径在巨噬细胞或嗜中性粒细胞吞噬后被诱导。相反，糖酵解基因在吞噬作用后不被诱导，并且在感染的肾脏中表达。所有三种途径的突变都减弱了这种真菌的毒力，突出了中心碳代谢对C。白色念珠菌感染我们得出结论：C.白色念珠菌显示出代谢程序，其中乙醛酸循环和糖异生在病原体被宿主细胞吞噬时被早期激活，而随后的全身性疾病的进展依赖于糖酵解。
To establish an infection, the pathogen Candida albicans must assimilate carbon and grow in its mammalian host. This fungus assimilates six-carbon compounds via the glycolytic pathway, and two-carbon compounds via the glyoxylate cycle and gluconeogenesis. We address a paradox regarding the roles of these central metabolic pathways in C. albicans pathogenesis: the glyoxylate cycle is apparently required for virulence although glyoxylate cycle genes are repressed by glucose at concentrations present in the bloodstream. Using GFP fusions, we confirm that glyoxylate cycle and gluconeogenic genes in C. albicans are repressed by physiologically relevant concentrations of glucose, and show that these genes are inactive in the majority of fungal cells infecting the mouse kidney. However, these pathways are induced following phagocytosis by macrophages or neutrophils. In contrast, glycolytic genes are not induced following phagocytosis and are expressed in infected kidney. Mutations in all three pathways attenuate the virulence of this fungus, highlighting the importance of central carbon metabolism for the establishment of C. albicans infections. We conclude that C. albicans displays a metabolic program whereby the glyoxylate cycle and gluconeogenesis are activated early, when the pathogen is phagocytosed by host cells, while the subsequent progression of systemic disease is dependent upon glycolysis.
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影响因子：
3
作者：
Dennison, PMJ;Ramsdale, M;Brown, AJP
通讯作者：
Brown, AJP
影响因子：
3.5
作者：
Leuker, CE;Sonneborn, A;Ernst, JF
通讯作者：
Ernst, JF
影响因子：
--
作者：
Lorenz, MC;Bender, JA;Fink, GR
通讯作者：
Fink, GR
DOI：
10.1073/pnas.1834481100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Rubin-Bejerano, I;Fraser, I;Fink, GR
通讯作者：
Fink, GR
影响因子：
3.1
作者：
Sundstrom, P;Cutler, JE;Staab, JF
通讯作者：
Staab, JF