Angiolella Letizia, Vitali Alberto, Stringaro Annarita, Mignogna Giuseppina, Maras Bruno, Bonito Mariantonietta, Colone Marisa, Palamara Anna Teresa, Cassone Antonio
Department of Public Health Sciences G. Sanarelli, University of Rome La Sapienza, Rome, Italy.
Int J Antimicrob Agents. 2009 Feb;33(2):143-8. doi: 10.1016/j.ijantimicag.2008.08.021. Epub 2008 Nov 14.
Several proteins are covalently bound to the cell wall glucan (glucan-associated proteins (GAPs)) in Candida albicans and different drugs may cause their modulation. Proteomic analysis is a suitable approach to study differential GAP patterns between control and drug-treated cells. Since antimycotics induce variation in GAP content, we investigated the effect of a sublethal dose of micafungin and observed a clear increase in Bgl2p, an enzyme with glucanosyltransferase activity, with respect to a general decrease in cell wall protein content. Immunoelectron microscopy using mouse antiserum confirmed this increase of Bgl2p on the outer cell wall but also revealed a dramatic increase in the immature Bgl2p isoform in the cytoplasm of drug-treated cells. Since this increased expression of Bgl2p is clearly dependent upon micafungin treatment, this enzyme appears to be one of the survival strategies of C. albicans and thus could be considered the molecular basis of antifungal resistance and also as a potential valuable candidate for future vaccine development.
在白色念珠菌中，几种蛋白质与细胞壁葡聚糖共价结合（葡聚糖相关蛋白，GAPs），不同药物可能会导致其发生调节。蛋白质组学分析是研究对照细胞和药物处理细胞之间GAP模式差异的合适方法。由于抗真菌药物会诱导GAP含量发生变化，我们研究了亚致死剂量的米卡芬净的作用，观察到具有葡聚糖基转移酶活性的酶Bgl2p明显增加，而细胞壁蛋白质含量总体下降。使用小鼠抗血清的免疫电子显微镜证实了Bgl2p在细胞外壁上的这种增加，但也揭示了药物处理细胞细胞质中未成熟Bgl2p异构体的显著增加。由于Bgl2p的这种表达增加明显依赖于米卡芬净处理，这种酶似乎是白色念珠菌的生存策略之一，因此可以被认为是抗真菌耐药性的分子基础，也是未来疫苗开发的潜在有价值候选物。
