Spiering Martin J, Moran Gary P, Chauvel Murielle, Maccallum Donna M, Higgins Judy, Hokamp Karsten, Yeomans Tim, d'Enfert Christophe, Coleman David C, Sullivan Derek J
Microbiology Research Unit, Division of Oral Biosciences, Dublin Dental School and Hospital, University of Dublin, Trinity College, Dublin 2, Ireland.
Eukaryot Cell. 2010 Feb;9(2):251-65. doi: 10.1128/EC.00291-09. Epub 2009 Dec 18.
Candida albicans and Candida dubliniensis are closely related species displaying differences in virulence and genome content, therefore providing potential opportunities to identify novel C. albicans virulence genes. C. albicans gene arrays were used for comparative analysis of global gene expression in the two species in reconstituted human oral epithelium (RHE). C. albicans (SC5314) showed upregulation of hypha-specific and virulence genes within 30 min postinoculation, coinciding with rapid induction of filamentation and increased RHE damage. C. dubliniensis (CD36) showed no detectable upregulation of hypha-specific genes, grew as yeast, and caused limited RHE damage. Several genes absent or highly divergent in C. dubliniensis were upregulated in C. albicans. One such gene, SFL2 (orf19.3969), encoding a putative heat shock factor, was deleted in C. albicans. DeltaDeltasfl2 cells failed to filament under a range of hypha-inducing conditions and exhibited greatly reduced RHE damage, reversed by reintroduction of SFL2 into the DeltaDeltasfl2 strain. Moreover, SFL2 overexpression in C. albicans triggered hyphal morphogenesis. Although SFL2 deletion had no apparent effect on host survival in the murine model of systemic infection, DeltaDeltasfl2 strain-infected kidney tissues contained only yeast cells. These results suggest a role for SFL2 in morphogenesis and an indirect role in C. albicans pathogenesis in epithelial tissues.
白色念珠菌和都柏林念珠菌是密切相关的物种，在毒力和基因组内容上存在差异，因此为鉴定新的白色念珠菌毒力基因提供了潜在机会。利用白色念珠菌基因阵列对这两个物种在重组人口腔上皮细胞（RHE）中的全局基因表达进行比较分析。白色念珠菌（SC5314）在接种后30分钟内显示出菌丝特异性基因和毒力基因的上调，这与丝状化的快速诱导和RHE损伤增加相一致。都柏林念珠菌（CD36）未检测到菌丝特异性基因的上调，以酵母形式生长，并导致有限的RHE损伤。在都柏林念珠菌中缺失或高度分化的几个基因在白色念珠菌中上调。其中一个基因SFL2（orf19.3969），编码一种假定的热休克因子，在白色念珠菌中被删除。DeltaDeltasfl2细胞在一系列菌丝诱导条件下无法形成菌丝，并且表现出RHE损伤大大减少，将SFL2重新引入DeltaDeltasfl2菌株可逆转这种情况。此外，白色念珠菌中SFL2的过表达引发了菌丝形态发生。虽然SFL2缺失对系统性感染小鼠模型中的宿主存活没有明显影响，但DeltaDeltasfl2菌株感染的肾脏组织中仅含有酵母细胞。这些结果表明SFL2在形态发生中起作用，并在白色念珠菌在上皮组织中的发病机制中起间接作用。
