PHR1, a pH-regulated gene of Candida albicans encoding a glucan-remodelling enzyme, is required for adhesion and invasion
PHR1, a pH-regulated gene of Candida albicans encoding a glucan-remodelling enzyme, is required for adhesion and invasion
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DOI：
10.1099/mic.0.038000-0
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发表时间：
2010-08-01
期刊：
影响因子：
2.8
通讯作者：
Popolo, Laura
中科院分区：
文献类型：
--
作者：
Calderon, Julia;Zavrel, Martin;Popolo, Laura
真菌细胞壁在宿主病原体相互作用中发挥着至关重要的作用，它的形成是几种细胞外酶协调活动的结果，这些酶组装成分，并在细胞外空间重塑和水解它们。白色念珠菌Phr 1和Phr 2蛋白属于β-（1，3）-葡聚糖基转移酶家族GH 72，在细胞壁组装中发挥着至关重要的作用。PHR 1和PHR 2，同源的酿酒酵母GAS 1，是不同的调节细胞外pH PHR 1的表达时，环境pH为5 5或更高，而PHR 2具有相反的表达模式。它们的缺失导致形态发生和毒力的pH条件缺陷。在这项工作中，我们探讨了PHR 1缺失是否影响白色念珠菌粘附和侵入人类上皮细胞的能力。PHR 1无效突变体对非生物表面和上皮细胞单层的粘附力显着降低。此外，突变体不能穿透和侵入重建的人上皮细胞。选择的菌丝特异性和粘附素编码基因的转录谱表明，在PHR 1无效突变体中，HWP 1和ECE 1转录水平在粘附和悬浮条件下都类似地降低。这些结果，结合隔膜位置的显微镜分析，表明PHR 1不是诱导菌丝发育所必需的，但在维持菌丝生长中起关键作用。Phr 1 p催化的3）-葡聚糖加工在维持白色念珠菌粘附和侵袭特性所依赖的形态学状态方面具有根本的重要性
The fungal cell wall plays a crucial role in host pathogen interactions Its formation is the result of the coordinated activity of several extracellular enzymes, which assemble the constituents, and remodel and hydrolyse them in the extracellular space Candida albicans Phr1 and Phr2 proteins belong to family GH72 of the beta-(1,3)-glucanosyltransferases and play a crucial role in cell wall assembly. PHR1 and PHR2, homologues of Saccharomyces cerevisiae GAS1, are differently regulated by extracellular pH PHR1 is expressed when ambient pH is 5 5 or higher, whereas PHR2 has the reverse expression pattern. Their deletion causes a pH-conditional defect in morphogenesis and virulence In this work we explored whether PHR1 deletion affects the ability of C albicans to adhere to and invade human epithelia PHR1 null mutants exhibited a marked reduction in adhesion to both abiotic surfaces and epithelial cell monolayers. In addition, the mutant was unable to penetrate and invade reconstituted human epithelia. Transcription profiling of selected hyphal-specific and adhesin-encoding genes indicated that in the PHR1 null mutant, HWP1 and ECE1 transcript levels were similarly reduced in both adhesion and suspension conditions These results, combined with microscopy analysis of the septum position, suggest that PHR1 is not required for the induction of hyphal development but plays a key role in the maintenance of hyphal growth Thus, the beta-(1,3)-glucan processing catalysed by Phr1p is of fundamental importance in the maintenance of the morphological state on which the adhesive and invasive properties of C albicans greatly depend