Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom.
Proteomics. 2012 Nov;12(21):3164-79. doi: 10.1002/pmic.201200228.
The major fungal pathogen Candida albicans can occupy diverse microenvironments in its human host. During colonization of the gastrointestinal or urogenital tracts, mucosal surfaces, bloodstream, and internal organs, C. albicans thrives in niches that differ with respect to available nutrients and local environmental stresses. Although most studies are performed on glucose-grown cells, changes in carbon source dramatically affect cell wall architecture, stress responses, and drug resistance. We show that growth on the physiologically relevant carboxylic acid, lactate, has a significant impact on the C. albicans cell wall proteome and secretome. The regulation of cell wall structural proteins (e.g. Cht1, Phr1, Phr2, Pir1) correlated with extensive cell wall remodeling in lactate-grown cells and with their increased resistance to stresses and antifungal drugs, compared with glucose-grown cells. Moreover, changes in other proteins (e.g. Als2, Gca1, Phr1, Sap9) correlated with the increased adherence and biofilm formation of lactate-grown cells. We identified mating and pheromone-regulated proteins that were exclusive to lactate-grown cells (e.g. Op4, Pga31, Pry1, Scw4, Yps7) as well as mucosa-specific and other niche-specific factors such as Lip4, Pga4, Plb5, and Sap7. The analysis of the corresponding null mutants confirmed that many of these proteins contribute to C. albicans adherence, stress, and antifungal drug resistance. Therefore, the cell wall proteome and secretome display considerable plasticity in response to carbon source. This plasticity influences important fitness and virulence attributes known to modulate the behavior of C. albicans in different host microenvironments during infection.
白色念珠菌是主要的真菌病原体，可以在人体宿主的各种微环境中生存。在胃肠道或泌尿生殖道、黏膜表面、血液和内部器官的定植过程中，白色念珠菌在营养物质和局部环境压力不同的小生境中茁壮成长。尽管大多数研究都是在葡萄糖培养的细胞上进行的，但碳源的变化会极大地影响细胞壁结构、应激反应和耐药性。我们发现，在生理相关的羧酸、乳酸上生长对白色念珠菌细胞壁蛋白质组和分泌组有显著影响。与葡萄糖培养的细胞相比，在乳酸培养的细胞中，细胞壁结构蛋白（如 Cht1、Phr1、Phr2、Pir1）的调节与广泛的细胞壁重塑相关，并且它们对压力和抗真菌药物的耐药性增加。此外，其他蛋白质（如 Als2、Gca1、Phr1、Sap9）的变化与乳酸培养的细胞黏附和生物膜形成的增加相关。我们鉴定了与乳酸生长的细胞中特有的交配和信息素调节蛋白（如 Op4、Pga31、Pry1、Scw4、Yps7）以及黏膜特异性和其他小生境特异性因子（如 Lip4、Pga4、Plb5 和 Sap7）。相应的缺失突变体分析证实，这些蛋白质中的许多都有助于白色念珠菌的黏附、应激和抗真菌药物耐药性。因此，细胞壁蛋白质组和分泌组在响应碳源时表现出相当大的可塑性。这种可塑性影响了重要的适应性和毒力属性，这些属性已知会调节白色念珠菌在感染过程中不同宿主微环境中的行为。
