Rouabhia Mahmoud, Schaller Martin, Corbucci Cristina, Vecchiarelli Anna, Prill Stephan K-H, Giasson Luc, Ernst Joachim F
Institut for Mikrobiologie, Universitätsstr. 1/26.12, 40225 Düsseldorf, Germany.
Infect Immun. 2005 Aug;73(8):4571-80. doi: 10.1128/IAI.73.8.4571-4580.2005.
The PMT gene family in Candida albicans encodes five isoforms of protein mannosyltransferases (Pmt proteins Pmt1p, Pmt2p, Pmt4p, Pmt5p, and Pmt6p) that initiate O mannosylation of secretory proteins. We compared virulence characteristics of pmt mutants in two complex, three-dimensional models of localized candidiasis, using reconstituted human epithelium (RHE) and engineered human oral mucosa (EHOM); in addition, mutants were tested in a mouse model of hematogenously disseminated candidiasis (HDC). All pmt mutants showed attenuated virulence in the HDC model and at least one model of localized candidiasis. The pmt5 mutant, which lacks in vitro growth phenotypes, was less virulent in the EHOM and HDC assays but had no consistent phenotype in the RHE assay. In contrast, the pmt4 and pmt6 mutants were less virulent in the RHE and HDC assays but not in the EHOM assay. The results stress the contribution of all Pmt isoforms to the virulence of C. albicans and suggest that the importance of individual Pmt isoforms may differ in specific host niches. We propose that Pmt proteins may be suitable targets for future novel classes of antifungal agents.
白色念珠菌中的PMT基因家族编码五种蛋白质甘露糖基转移酶同工型（Pmt蛋白Pmt1p、Pmt2p、Pmt4p、Pmt5p和Pmt6p），这些同工型启动分泌蛋白的O-甘露糖基化。我们使用重组人上皮细胞（RHE）和工程化人口腔黏膜（EHOM），在两种复杂的、三维的局部念珠菌病模型中比较了pmt突变体的毒力特征；此外，还在血源性播散性念珠菌病（HDC）小鼠模型中对突变体进行了测试。所有pmt突变体在HDC模型和至少一种局部念珠菌病模型中均表现出毒力减弱。缺乏体外生长表型的pmt5突变体在EHOM和HDC试验中毒力较低，但在RHE试验中没有一致的表型。相比之下，pmt4和pmt6突变体在RHE和HDC试验中毒力较低，但在EHOM试验中则不然。结果强调了所有Pmt同工型对白色念珠菌毒力的贡献，并表明单个Pmt同工型的重要性在特定宿主生态位中可能有所不同。我们提出，Pmt蛋白可能是未来新型抗真菌药物的合适靶点。
