Visualizing fungal infections in living mice using bioluminescent pathogenic Candida albicans strains transformed with the firefly luciferase gene
Visualizing fungal infections in living mice using bioluminescent pathogenic Candida albicans strains transformed with the firefly luciferase gene
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DOI：
10.1016/j.micpath.2005.11.003
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发表时间：
2006-02-01
影响因子：
3.8
通讯作者：
Contag, PR
中科院分区：
文献类型：
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作者：
Doyle, TC;Nawotka, KA;Contag, PR
白色念珠菌的动物研究为了解真菌毒力和抗真菌药物开发提供了模型。为了无创监测长期念珠菌鼠感染，用密码子优化的荧光素酶基因稳定转化临床分离株，以组成型表达荧光素酶。在带有工程菌株的小鼠中建立了慢性全身感染，并且通过使用电荷耦合设备相机的非侵入性成像，肾脏发出了明显的生物发光信号。这些感染是在免疫能力强的小鼠中建立的，并且在没有表现出感染的生理后果的动物以及那些视觉上死于该疾病的动物中可以检测到生物发光。同样，从阴道感染的小鼠的阴道组织中测量生物发光。通过平板阴道灌洗液测定的真菌负荷显示出与测量的生物发光信号相似的模式，并且通过这两种方式感染后 30 多天都可以在动物中检测到真菌感染。在该模型中测试了抗真菌药物咪康唑的效果，通过直接成像和真菌负荷测定，动物体内的清除率是显而易见的。使用生物发光来监测这些和其他念珠菌感染模型将大大加快药物开发研究的分析速度，既易于可视化感染，又可减少进行此类研究所需的动物数量。 (c) 2005 Elsevier Ltd. 保留所有权利。
Animal studies with Candida albicans have provided models for understanding fungal virulence and antifungal drug development. To noninvasively monitor long-term Candida murine infections, clinical isolates were stably transformed with a codon-optimized luciferase gene to constitutively express luciferase. Chronic systemic infections were established in mice with engineered strains, and bioluminescent signals were apparent from kidneys by non-invasive imaging using charged-coupled device cameras. These infections were established in immune-competent mice, and bioluminescence was detectable in animals that showed no physiological consequence of infection, as well as those visually succumbing to the disease. Similarly, bioluminescence was measured from the vaginal tissue of mice infected vaginally. Fungal loads determined by plating vaginal lavages showed a similar pattern to the bioluminescent signals measured, and fungal infection could be detected in animals for over 30 days post infection by both modalities. The effect of the antifungal drug miconazole was tested in this model, and clearance in animals was apparent by both direct imaging and fungal load determination. The use of bioluminescence to monitor these and other models of Candida infections will greatly speed up the analysis of drug development studies, both in ease of visualizing infections and decreasing numbers of animals required to run such studies. (c) 2005 Elsevier Ltd. All rights reserved.