Carvalho-Pereira Joana, Vaz Catarina, Carneiro Catarina, Pais Célia, Sampaio Paula
Biology Department, Minho University, Campus de Gualtar, 4710-057 Braga, Portugal.
Biomed Res Int. 2015;2015:148343. doi: 10.1155/2015/148343. Epub 2015 Feb 4.
The secreted aspartic proteases (Saps) are among the most studied virulence determinants in Candida albicans. These proteins are translated as pre-pro-enzymes consisting of a signal sequence followed by a propeptide and the mature enzyme. The propeptides of secreted proteinases are important for the correct processing, folding/secretion of the mature enzyme. In this study, the DNA sequences of C. albicans Saps were screened and a microsatellite was identified in SAP8 propeptide region. The genetic variability of the repetitive region of Sap8 propeptide was determined in 108 C. albicans independent strains isolated from different types of infection: oral infection (OI), oral commensal (OC), vulvovaginal candidiasis (VVC), and bloodstream infections (BSI). Nine different propeptides for Sap8 processing were identified whose frequencies varied with the type of infection. OC strains presented the highest gene diversity while OI isolated the lowest. The contribution of the Saps to mucosal and systemic infections has been demonstrated and recently Sap8 has been implicated in the cleavage of a signalling glycoprotein that leads to Cek1-MAPK pathway activation. This work is the first to identify a variable microsatellite in the propeptide of a secreted aspartic protease and brings new insights into the variability of Sap8.
分泌型天冬氨酸蛋白酶(Saps)是白色念珠菌中研究最多的毒力决定因素之一。这些蛋白质被翻译为前体酶原,由信号序列、前肽和成熟酶组成。分泌型蛋白酶的前肽对于成熟酶的正确加工、折叠/分泌很重要。在本研究中,对白色念珠菌Saps的DNA序列进行了筛选,并在SAP8前肽区域鉴定出一个微卫星。在从不同类型感染中分离出的108株白色念珠菌独立菌株中,测定了Sap8前肽重复区域的遗传变异性,这些感染类型包括口腔感染(OI)、口腔共生菌(OC)、外阴阴道念珠菌病(VVC)和血流感染(BSI)。鉴定出了9种不同的用于Sap8加工的前肽,其频率随感染类型而变化。OC菌株呈现出最高的基因多样性,而OI分离株的基因多样性最低。Saps对黏膜和全身感染的作用已得到证实,最近Sap8被认为与一种信号糖蛋白的裂解有关,该裂解导致Cek1-MAPK途径激活。这项工作首次在分泌型天冬氨酸蛋白酶的前肽中鉴定出一个可变微卫星,并为Sap8的变异性带来了新的见解。