Dos Santos André Luis Souza
André Luis Souza dos Santos, Laboratory of Multidisciplinary Studies on Microbial Biochemistry, Department of General Microbiology, Institute of Microbiology Prof. Paulo de Góes, Federal University of Rio de Janeiro, Rio de Janeiro, RJ 21941-902, Brazil.
World J Biol Chem. 2010 Feb 26;1(2):21-30. doi: 10.4331/wjbc.v1.i2.21.
Cells of Candida albicans (C. albicans) can invade humans and may lead to mucosal and skin infections or to deep-seated mycoses of almost all inner organs, especially in immunocompromised patients. In this context, both the host immune status and the ability of C. albicans to modulate the expression of its virulence factors are relevant aspects that drive the candidal susceptibility or resistance; in this last case, culminating in the establishment of successful infection known as candidiasis. C. albicans possesses a potent armamentarium consisting of several virulence molecules that help the fungal cells to escape of the host immune responses. There is no doubt that the secretion of aspartyl-type proteases, designated as Saps, are one of the major virulence attributes produced by C. albicans cells, since these hydrolytic enzymes participate in a wide range of fungal physiological processes as well as in different facets of the fungal-host interactions. For these reasons, Saps clearly hold promise as new potential drug targets. Corroborating this hypothesis, the introduction of new anti-human immunodeficiency virus drugs of the aspartyl protease inhibitor-type (HIV PIs) have emerged as new agents for the inhibition of Saps. The introduction of HIV PIs has revolutionized the treatment of HIV disease, reducing opportunistic infections, especially candidiasis. The attenuation of candidal infections in HIV-infected individuals might not solely have resulted from improved immunological status, but also as a result of direct inhibition of C. albicans Saps. In this article, we review updates on the beneficial effects of HIV PIs against the human fungal pathogen C. albicans, focusing on the effects of these compounds on Sap activity, growth behavior, morphological architecture, cellular differentiation, fungal adhesion to animal cells and abiotic materials, modulation of virulence factors, experimental candidiasis infection, and their synergistic actions with classical antifungal agents.
白色念珠菌（白假丝酵母）细胞可侵袭人体，可能导致黏膜和皮肤感染，或引发几乎所有内脏器官的深部真菌病，尤其是在免疫功能低下的患者中。在这种情况下，宿主的免疫状态以及白假丝酵母调节其毒力因子表达的能力都是影响念珠菌易感性或抗性的相关因素；在后一种情况下，最终会导致成功感染，即念珠菌病的发生。白假丝酵母拥有一系列强大的武器库，其中包含多种毒力分子，这些分子有助于真菌细胞逃避宿主的免疫反应。毫无疑问，天冬氨酸型蛋白酶（称为Saps）的分泌是白假丝酵母细胞产生的主要毒力属性之一，因为这些水解酶参与了广泛的真菌生理过程以及真菌与宿主相互作用的不同方面。基于这些原因，Saps显然有望成为新的潜在药物靶点。证实这一假设的是，天冬氨酸蛋白酶抑制剂型（HIV PIs）新型抗人类免疫缺陷病毒药物已成为抑制Saps的新药物。HIV PIs的引入彻底改变了HIV疾病的治疗方式，减少了机会性感染，尤其是念珠菌病。HIV感染个体中念珠菌感染的减轻可能不仅是由于免疫状态的改善，还可能是由于对白假丝酵母Saps的直接抑制。在本文中，我们综述了HIV PIs对人类真菌病原体白假丝酵母的有益作用的最新进展，重点关注这些化合物对Sap活性、生长行为、形态结构、细胞分化、真菌与动物细胞及非生物材料的黏附、毒力因子调节、实验性念珠菌感染的影响，以及它们与经典抗真菌药物的协同作用。
