Mycology Reference Laboratory, National Centre for Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
PLoS One. 2013;8(3):e60047. doi: 10.1371/journal.pone.0060047. Epub 2013 Mar 28.
The incidence of opportunistic fungal infections has increased in recent decades due to the growing proportion of immunocompromised patients in our society. Candida krusei has been described as a causative agent of disseminated fungal infections in susceptible patients. Although its prevalence remains low among yeast infections (2-5%), its intrinsic resistance to fluconazole makes this yeast important from epidemiologic aspects. Non mammalian organisms are feasible models to study fungal virulence and drug efficacy. In this work we have used the lepidopteran Galleria mellonella and the nematode Caenorhabditis elegans as models to assess antifungal efficacy during infection by C. krusei. This yeast killed G. mellonella at 25, 30 and 37°C and reduced haemocytic density. Infected larvae melanized in a dose-dependent manner. Fluconazole did not protect against C. krusei infection, in contrast to amphotericin B, voriconazole or caspofungin. However, the doses of these antifungals required to obtain larvae protection were always higher during C. krusei infection than during C. albicans infection. Similar results were found in the model host C. elegans. Our work demonstrates that non mammalian models are useful tools to investigate in vivo antifungal efficacy and virulence of C. krusei.
近年来，由于我们社会中免疫功能低下患者的比例不断增加，机会性真菌感染的发病率有所增加。克柔假丝酵母菌已被描述为易感患者播散性真菌感染的病原体。尽管其在酵母感染中的患病率（2-5%）仍然较低，但它对氟康唑的固有耐药性使其在流行病学方面具有重要意义。非哺乳动物生物是研究真菌毒力和药物疗效的可行模型。在这项工作中，我们使用鳞翅目昆虫家蚕和线虫秀丽隐杆线虫作为模型，评估克柔假丝酵母菌感染期间的抗真菌疗效。该酵母在 25、30 和 37°C 时可杀死家蚕并降低血淋巴细胞密度。受感染的幼虫以剂量依赖性方式黑化。氟康唑不能预防克柔假丝酵母菌感染，而两性霉素 B、伏立康唑或卡泊芬净则可以。然而，与白色念珠菌感染相比，在克柔假丝酵母菌感染期间，获得幼虫保护所需的这些抗真菌药物剂量始终更高。在模式宿主秀丽隐杆线虫中也发现了类似的结果。我们的工作表明，非哺乳动物模型是研究克柔假丝酵母菌体内抗真菌疗效和毒力的有用工具。
