酿酒酵母Rix7p(YLL034c)的白色念珠菌AAA型ATP酶同源物对于正常形态、生物膜形成以及分泌天冬氨酸蛋白酶的活性至关重要。

The Candida albicans AAA ATPase homologue of Saccharomyces cerevisiae Rix7p (YLL034c) is essential for proper morphology, biofilm formation and activity of secreted aspartyl proteinases.

作者信息

Melo A S A, Padovan A C B, Serafim R C, Puzer L, Carmona A K, Juliano Neto L, Brunstein A, Briones M R S

机构信息

Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo, São Paulo, SP, Brasil.

出版信息

Genet Mol Res. 2006 Nov 30;5(4):664-87.

DOI:
Abstract

Proper morphology is essential for the ability of Candida albicans to switch between yeast and hyphae and thereby sustain its virulence. Here we identified, by differential screening, a novel C. albicans AAA ATPase encoding gene, CaYLL34 (RIX7), with enhanced expression in hyphae. Phylogenetic analysis suggests that CaYLL34 belongs to a "VCP-like" subgroup of AAA ATPases essential for yeast viability and contains a bipartite nuclear localization signal. Inactivation of one copy of CaYLL34, by the URA-Blaster method, generated the heterozygous mutant strain M61. This strain has severe phenotypic alterations, such as a highly increased vacuole, abnormal cell shape and reduced growth in different conditions. Also, major pathogenicity factors are affected in M61, for instance, a significant decrease of hypha formation (>90%), surface biofilm adhesion (86%) and secreted aspartyl proteinase activity (76.5%). Our results show that the partial impairment of CaYll34p cellular levels is sufficient to affect the proper cellular morphology and pathogenicity factors and suggest that this protein is required for biogenesis of ribosomal subunits. Accordingly, we propose that the product of CaYLL34 could be tested as a novel target for antifungal drugs.

摘要

合适的形态对于白色念珠菌在酵母和菌丝之间转换的能力至关重要,从而维持其毒力。在这里,我们通过差异筛选鉴定了一个新的白色念珠菌AAA型ATP酶编码基因CaYLL34(RIX7),其在菌丝中表达增强。系统发育分析表明,CaYLL34属于对酵母生存能力至关重要的AAA型ATP酶的“VCP样”亚组,并含有一个双分型核定位信号。通过URA-Blaster方法使CaYLL34的一个拷贝失活,产生了杂合突变株M61。该菌株具有严重的表型改变,如液泡高度增加、细胞形状异常以及在不同条件下生长减少。此外,主要致病因子在M61中受到影响,例如,菌丝形成显著减少(>90%)、表面生物膜粘附(86%)和分泌天冬氨酸蛋白酶活性(76.5%)。我们的结果表明,CaYll34p细胞水平的部分损害足以影响细胞的正常形态和致病因子,并表明该蛋白是核糖体亚基生物合成所必需的。因此,我们建议可以将CaYLL34的产物作为抗真菌药物的新靶点进行测试。

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