Ng T T, Robson G D, Denning D W
Department of Microbiology, Hope Hospital, Salford, UK.
Microbiology (Reading). 1994 Sep;140 ( Pt 9):2475-9. doi: 10.1099/13500872-140-9-2475.
Aspergillus fumigatus and Aspergillus flavus are the most common cause of invasive mould infections worldwide and carry a high mortality. Corticosteroid therapy and Cushing's disease are associated with an increase in invasive aspergillosis. Corticosteroids impair immune function in mammals and, specifically, the conidicidal activity of human macrophages, which was thought to be sufficient explanation for this increased risk. However, we have found a 30-40% increase in growth rate of A. fumigatus and A. flavus exposed to pharmacological doses of hydrocortisone (a human glucocorticoid), suggesting an alternative or additional mechanism for the association. No significant effect was observed with other human steroids such as testosterone, oestradiol or progesterone, though a smaller (21%) but significant growth rate increase was obtained with the fungal sterol ergosterol. The presence of a ligand/receptor system is therefore possible in pathogenic Aspergillus spp. Although corticosterone-binding proteins have been identified in some yeast species, a demonstrable physiological effect has been lacking. Interruption of the putative ligand/receptor interaction could have a major effect on the growth and pathogenicity of A. fumigatus, providing opportunities for the development of alternative therapeutic strategies to those currently available.
烟曲霉和黄曲霉是全球侵袭性霉菌感染的最常见病因，死亡率很高。皮质类固醇疗法和库欣病与侵袭性曲霉病的增加有关。皮质类固醇会损害哺乳动物的免疫功能，特别是人类巨噬细胞的杀分生孢子活性，这被认为足以解释这种风险增加的原因。然而，我们发现，暴露于药理剂量氢化可的松（一种人类糖皮质激素）的烟曲霉和黄曲霉的生长速率提高了30%-40%，这表明存在另一种或额外的关联机制。其他人类类固醇，如睾酮、雌二醇或孕酮，未观察到显著影响，不过真菌固醇麦角固醇使生长速率有较小幅度（21%）但显著的增加。因此，致病性曲霉属中可能存在配体/受体系统。虽然在一些酵母物种中已鉴定出皮质酮结合蛋白，但一直缺乏可证明的生理效应。中断假定的配体/受体相互作用可能对烟曲霉的生长和致病性产生重大影响，为开发不同于现有疗法的替代治疗策略提供了机会。
