Development and Validation of an In Vivo Candida albicans Biofilm Denture Model
Development and Validation of an In Vivo Candida albicans Biofilm Denture Model
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DOI：
10.1128/iai.00480-10
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发表时间：
2010-09-01
影响因子：
3.1
通讯作者：
Andes, David R.
中科院分区：
文献类型：
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作者：
Nett, Jeniel E.;Marchillo, Karen;Andes, David R.
口腔念珠菌病最常见的形式是假牙相关性口腔炎，涉及口腔修复体表面生物膜的生长。这种独特环境中的细胞能够抵御宿主防御并在抗真菌治疗中存活下来。对假牙生物膜过程的研究主要限于体外模型。我们开发了啮齿动物丙烯酸假牙模型，并使用时程定量培养实验、共聚焦显微镜、扫描电子显微镜和抗真菌药敏测定来表征白色念珠菌和混合口腔细菌菌群生物膜的形成、结构和体内耐药性。我们还检查了该模型在测量白色念珠菌基因表达方面的实用性，并测试了特定基因产物 (Bcr1p) 对生物膜形成的影响。最后，我们评估了粘膜宿主对假牙生物膜的反应，发现粘膜组织病理学与急性人类假牙口腔炎一致，表明真菌入侵和中性粒细胞浸润。目前的口腔假牙模型模拟了人类假牙口腔炎，应该有助于测试基因破坏对生物膜形成的影响，研究抗感染药物的影响，检查念珠菌-口腔细菌菌群生物膜混合感染的生物学，以及表征宿主对该疾病过程的免疫反应。
The most common form of oral candidiasis, denture-associated stomatitis, involves biofilm growth on an oral prosthetic surface. Cells in this unique environment are equipped to withstand host defenses and survive antifungal therapy. Studies of the biofilm process on dentures have primarily been limited to in vitro models. We developed a rodent acrylic denture model and characterized the Candida albicans and mixed oral bacterial flora biofilm formation, architecture, and drug resistance in vivo, using time course quantitative culture experiments, confocal microscopy, scanning electron microscopy, and antifungal susceptibility assays. We also examined the utility of the model for measurement of C. albicans gene expression and tested the impact of a specific gene product (Bcr1p) on biofilm formation. Finally, we assessed the mucosal host response to the denture biofilm and found the mucosal histopathology to be consistent with that of acute human denture stomatitis, demonstrating fungal invasion and neutrophil infiltration. This current oral denture model mimics human denture stomatitis and should be useful for testing the impact of gene disruption on biofilm formation, studying the impact of anti-infectives, examining the biology of mixed Candida-oral bacterial flora biofilm infections, and characterizing the host immunologic response to this disease process.