Centre for Infectious Diseases and Microbiology, Westmead Hospital, University of Sydney, Westmead, NSW Australia.
Virulence. 2011 Jul-Aug;2(4):280-95. doi: 10.4161/viru.2.4.16764. Epub 2011 Jul 1.
Conventional antineoplastic, novel immunosuppressive agents and antibiotics used in cancer treatment can directly affect the growth, development and virulence of Candida and Aspergillus species. Cytotoxic and cisplatin compounds have anti-Candida activity and may be synergistic with antifungal drugs; they also inhibit Candida and Aspergillus filamentation/conidation and effect increased virulence in vitro. Glucocorticoids enhance Candida adherence to epithelial cells, germination in serum and in vitro secretion of phospholipases and proteases, as well as growth of A. fumigatus. Calcineurin and target of rapamycin inhibitors perturb Candida and Aspergillus morphogenesis, stress responses and survival in serum, reduce azole tolerance in Candida, but yield conflicting in vivo data. Inhibition of candidal heat shock protein 90 and candidal-specific histone deacetylase represent feasible therapeutic approaches for candidiasis. Tyrosine kinase inhibitors inhibit fungal cell entry into epithelial cells and phagocytosis. Quinolone and other antibiotics may augment activity of azole and polyene agents. The correlation of in vitro effects with clinically meaningful in vivo systems is warranted.
用于癌症治疗的常规抗肿瘤药物、新型免疫抑制剂和抗生素可直接影响念珠菌属和曲霉属的生长、发育和毒力。细胞毒性和顺铂化合物具有抗真菌活性，可能与抗真菌药物具有协同作用；它们还抑制念珠菌属和曲霉属的丝状/产孢和体外毒力。糖皮质激素增强了念珠菌对上皮细胞的黏附、在血清中的发芽以及磷脂酶和蛋白酶的体外分泌，同时促进了烟曲霉的生长。钙调神经磷酸酶和雷帕霉素靶蛋白抑制剂扰乱了念珠菌属和曲霉属的形态发生、应激反应和在血清中的存活，降低了念珠菌对唑类药物的耐受性，但在体内产生了相互矛盾的数据。抑制真菌热休克蛋白 90 和真菌特异性组蛋白去乙酰化酶是治疗念珠菌病的可行方法。酪氨酸激酶抑制剂抑制真菌细胞进入上皮细胞和吞噬作用。喹诺酮类和其他抗生素可能增强唑类和多烯类药物的活性。有必要将体外作用与临床有意义的体内系统相关联。
