Schweizer A, Rupp S, Taylor B N, Röllinghoff M, Schröppel K
Institute of Clinical Microbiology, Immunology and Hygiene, University of Erlangen, Wasserturmstrasse 3, 91054 Erlangen, Germany.
Mol Microbiol. 2000 Nov;38(3):435-45. doi: 10.1046/j.1365-2958.2000.02132.x.
The temporal and spatial expression of stage-specific genes during morphological development of fungi and higher eukaryotes is controlled by transcription factors. In this study, we report the cloning and functional analysis of the Candida albicans TEC1 (CaTEC1) gene, a new member of the TEA/ATTS family of transcription factors that regulates C. albicans virulence. The promoters of the type 4, 5 and 6 proteinase isogenes (SAP4-6) contain repetitive TEA/ATTS consensus sequence motifs. This finding suggests a possible role for a homologue of Saccharomyces cerevisiae TEC1 during the activation of proteinase gene expression in C. albicans. CaTEC1 is predominantly expressed in the hyphal form of C. albicans. In vitro, serum-induced hyphal formation as well as evasion from MPhi after phagocytosis is suppressed in catec1/catec1 mutant cells. Furthermore, expression of the proteinase isogenes SAP4-6 is no longer inducible in these mutant cells. The deletion of the CaTEC1 gene attenuates virulence of C. albicans in a systemic model of murine candidiasis, although both mutant and revertant cells that were prepared from infected tissues or the vaginal mucosa grew in a hyphal morphology in vivo. CaTEC1 complements the pseudohyphal and invasive growth defect of haploid and diploid S. cerevisiae tec1/tec1 mutant cells and strongly activates the promoter of FLO11, a gene required for pseudohyphal growth. This study provides the first evidence pointing to an essential role for a member of the TEA/ATTS transcription factor family that had so far only been ascribed to function during development as a virulence regulator in microbial pathogenesis.
真菌和高等真核生物形态发育过程中阶段特异性基因的时空表达受转录因子控制。在本研究中，我们报道了白色念珠菌TEC1（CaTEC1）基因的克隆及功能分析，该基因是调节白色念珠菌毒力的TEA/ATTS转录因子家族的新成员。4型、5型和6型蛋白酶同基因（SAP4 - 6）的启动子含有重复的TEA/ATTS共有序列基序。这一发现表明酿酒酵母TEC1的同源物在白色念珠菌蛋白酶基因表达激活过程中可能发挥作用。CaTEC1主要在白色念珠菌的菌丝形态中表达。在体外，catec1/catec1突变细胞中血清诱导的菌丝形成以及吞噬后逃避巨噬细胞的能力受到抑制。此外，这些突变细胞中蛋白酶同基因SAP4 - 6的表达不再可诱导。CaTEC1基因的缺失减弱了白色念珠菌在小鼠念珠菌病全身模型中的毒力，尽管从感染组织或阴道黏膜制备的突变细胞和回复细胞在体内均呈菌丝形态生长。CaTEC1弥补了单倍体和二倍体酿酒酵母tec1/tec1突变细胞的假菌丝和侵袭性生长缺陷，并强烈激活FLO11的启动子，FLO11是假菌丝生长所需的基因。本研究首次证明了TEA/ATTS转录因子家族成员的重要作用，该家族成员迄今为止仅被认为在发育过程中作为微生物发病机制中的毒力调节因子发挥作用。
