Zhang Ningxin, Harrex Annette L, Holland Barbara R, Fenton Lauren E, Cannon Richard D, Schmid Jan
Institute of Molecular BioSciences, Massey University, Palmerston North, New Zealand.
Genome Res. 2003 Sep;13(9):2005-17. doi: 10.1101/gr.1024903.
The ALS (agglutinin-like sequence) gene family encodes proteins that play a role in adherence of the yeast Candida albicans to endothelial and epithelial cells. The proteins are proposed as virulence factors for this important fungal pathogen of humans. We analyzed 66 C. albicans strains, representing a worldwide collection of 266 infection-causing isolates, and discovered 60 alleles of the ALS7 open reading frame (ORF). Differences between alleles were largely caused by rearrangements of repeat elements in the so-called tandem repeat domain (21 different types occurred) and the VASES region (19 different types). C. albicans is diploid, and combinations of ALS7 alleles generated 49 different genotypes. ALS7 expression was detected in samples isolated directly from five oral candidosis patients. ORFs in the opposite direction contained within the ALS7 ORF were also transcribed in all strains tested. Isolates representing a more pathogenic general-purpose genotype (GPG) cluster of strains tended to have more tandem repeats than other strains. Two types of VASES regions were largely exclusive to GPG strains; the remaining types were largely exclusive to noncluster strains. Our results provide evidence that ALS7 is a hypermutable contingency locus and important for the success of C. albicans as an opportunistic pathogen of humans.
类凝集素序列（ALS）基因家族编码的蛋白质在白色念珠菌粘附内皮细胞和上皮细胞过程中发挥作用。这些蛋白质被认为是这种人类重要真菌病原体的毒力因子。我们分析了66株白色念珠菌，它们代表了来自世界各地的266株致病分离株，并发现了ALS7开放阅读框（ORF）的60个等位基因。等位基因之间的差异主要是由所谓串联重复结构域（出现了21种不同类型）和VASES区域（出现了19种不同类型）中重复元件的重排引起的。白色念珠菌是二倍体，ALS7等位基因的组合产生了49种不同的基因型。在直接从5例口腔念珠菌病患者分离的样本中检测到了ALS7的表达。在所有测试菌株中，ALS7开放阅读框内相反方向的开放阅读框也被转录。代表更具致病性的通用基因型（GPG）菌株簇的分离株往往比其他菌株具有更多的串联重复。两种类型的VASES区域在很大程度上是GPG菌株所特有的；其余类型在很大程度上是无簇菌株所特有的。我们的结果提供了证据，表明ALS7是一个高度可变的应急位点，对白色念珠菌作为人类机会性病原体的成功起着重要作用。
