Carbon source-induced reprogramming of the cell wall proteome and secretome modulates the adherence and drug resistance of the fungal pathogen Candida albicans.
Carbon source-induced reprogramming of the cell wall proteome and secretome modulates the adherence and drug resistance of the fungal pathogen Candida albicans.
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碳源引起的细胞壁蛋白质组和分泌组的重编程可调节真菌病原体白色念珠菌的粘附和耐药性。
DOI：
10.1002/pmic.201200228
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发表时间：
2012-11
期刊：
影响因子：
3.4
通讯作者：
Brown, Alistair J. P.
中科院分区：
文献类型：
--
作者：
Ene, Iuliana V.;Heilmann, Clemens J.;Sorgo, Alice G.;Walker, Louise A.;de Koster, Chris G.;Munro, Carol A.;Klis, Frans M.;Brown, Alistair J. P.
主要的真菌病原体白色念珠菌可以占据不同的微环境，在其人类宿主。在胃肠道、泌尿生殖道、粘膜表面、血液和内脏器官的定植过程中，C.白色念珠菌在可利用的营养物和局部环境压力不同的小生境中生长。虽然大多数研究都是在葡萄糖生长的细胞上进行的，但碳源的变化会显着影响细胞壁结构，应激反应和耐药性。我们发现，生长在生理相关的羧酸，乳酸，有显着影响的C。白念珠菌细胞壁蛋白质组和分泌蛋白质组。与葡萄糖生长的细胞相比，细胞壁结构蛋白（例如Cht1，Phr1，Phr2，Pir1）的调节与乳酸盐生长的细胞中广泛的细胞壁重塑相关，并且与其对应力和抗真菌药物的抗性增加相关。此外，其他蛋白质（如Als2，Gca1，Phr1，Sap9）的变化与乳酸盐生长的细胞的粘附和生物膜形成的增加相关。我们确定了交配和信息素调节的蛋白质，这些蛋白质是乳酸盐生长的细胞所独有的（例如Op4，Pga31，Pry1，Scw4，Yps7），以及粘膜特异性和其他生态位特异性因子，如Lip4，Pga4，Plb5和Sap7。对相应的无效突变体的分析证实，这些蛋白质中的许多有助于C。白念珠菌粘附、应激和抗真菌药物耐药性。因此，细胞壁蛋白质组和分泌蛋白质组对碳源的响应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性属性，已知调节C。白念珠菌在不同的宿主微环境中感染。
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.
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影响因子：
3.4
作者：
Barelle CJ;Priest CL;Maccallum DM;Gow NA;Odds FC;Brown AJ
通讯作者：
Brown AJ
影响因子：
2.8
作者：
Calderon, Julia;Zavrel, Martin;Popolo, Laura
通讯作者：
Popolo, Laura
影响因子：
3.1
作者：
Hornbach, Anke;Heyken, Antje;Kurzai, Oliver
通讯作者：
Kurzai, Oliver
影响因子：
3
作者：
Dennison, PMJ;Ramsdale, M;Brown, AJP
通讯作者：
Brown, AJP
影响因子：
5.6
作者：
Eisenhaber, B;Schneider, G;Eisenhaber, F
通讯作者：
Eisenhaber, F