CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans.
CO(2) acts as a signalling molecule in populations of the fungal pathogen Candida albicans.
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DOI：
10.1371/journal.ppat.1001193
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发表时间：
2010-11-18
期刊：
影响因子：
6.7
通讯作者：
Mühlschlegel FA
中科院分区：
文献类型：
--
作者：
Hall RA;De Sordi L;Maccallum DM;Topal H;Eaton R;Bloor JW;Robinson GK;Levin LR;Buck J;Wang Y;Gow NA;Steegborn C;Mühlschlegel FA
当定殖宿主壁龛或非动画医疗设备时，真菌病原体白色念珠菌的单个细胞扩展成显著的生物质。在这里，我们表明，在这样的生物量，真菌代谢产生的CO2作为一个通信分子促进开关从酵母到丝状生长所必需的C。白色念珠菌病理学我们发现，CO2介导的菌落内信号转导涉及腺苷酸环化酶蛋白（Cyr 1 p），一个多传感器最近发现，以协调真菌对血清和细菌肽聚糖的反应。我们进一步确定了赖氨酸1373对Cyr 1 p的CO2/碳酸氢盐调节至关重要。CO2/碳酸氢盐受体位点的破坏选择性地干扰C.白色念珠菌在真菌生物质中的表达。黑腹果蝇感染模型和播散性念珠菌病小鼠模型之间的比较表明，代谢CO2传感可能是重要的初始殖民化和上皮入侵。我们的研究结果揭示了存在的气体念珠菌信号通路及其分子机制，并提供了一个进化保守的CO2信号系统的见解。病原微生物可以产生多种次级代谢物和信号分子，这些分子可以影响宿主，或者为它们提供对抗竞争性寄生生物的选择性优势。我们表明，气态的，代谢产生的CO2可以作为一个信号分子，以提高生物体的毒力感染建立过程中使用的真菌病原体白色念珠菌作为一个模型。此外，我们确定了可溶性腺苷酸环化酶，Cyr 1 p，这是至关重要的CO2传感，因此毒力的有机体的催化结构域内的CO2受体网站。CO2传感在多种致病物种中是保守的，并且已经显示增加的水平抑制宿主的免疫系统。因此，CO2传感可能代表了一种机制，以提高C。当宿主的免疫系统受到抑制时，白色念珠菌的毒力就会下降。
When colonising host-niches or non-animated medical devices, individual cells of the fungal pathogen Candida albicans expand into significant biomasses. Here we show that within such biomasses, fungal metabolically generated CO2 acts as a communication molecule promoting the switch from yeast to filamentous growth essential for C. albicans pathology. We find that CO2-mediated intra-colony signalling involves the adenylyl cyclase protein (Cyr1p), a multi-sensor recently found to coordinate fungal responses to serum and bacterial peptidoglycan. We further identify Lys 1373 as essential for CO2/bicarbonate regulation of Cyr1p. Disruption of the CO2/bicarbonate receptor-site interferes selectively with C. albicans filamentation within fungal biomasses. Comparisons between the Drosophila melanogaster infection model and the mouse model of disseminated candidiasis, suggest that metabolic CO2 sensing may be important for initial colonisation and epithelial invasion. Our results reveal the existence of a gaseous Candida signalling pathway and its molecular mechanism and provide insights into an evolutionary conserved CO2-signalling system. Pathogenic microorganisms can produce a variety of secondary metabolites and signalling molecules which can affect the host, or provide them with a selective advantage against competing commensal organisms. We demonstrate that gaseous, metabolically generated CO2 can serve as a signalling molecule to enhance the organism's virulence during infection establishment by using the fungal pathogen Candida albicans as a model. Furthermore, we identified a CO2 receptor site within the catalytic domain of the soluble adenylyl cyclase, Cyr1p, which is critical for CO2 sensing and hence virulence of the organism. CO2 sensing is conserved in a variety of pathogenic species, and increased levels have been shown to suppress the host's immune system. Thus, CO2 sensing may represent a mechanism to enhance C. albicans virulence when the host's immune system is suppressed.
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影响因子：
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