Nett Jeniel E, Brooks Erin G, Cabezas-Olcoz Jonathan, Sanchez Hiram, Zarnowski Robert, Marchillo Karen, Andes David R
Department of Medicine, University of Wisconsin, Madison, Wisconsin, USA Department of Medical Microbiology and Immunology, University of Wisconsin, Madison, Wisconsin, USA.
Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin, USA.
Infect Immun. 2014 Dec;82(12):4931-40. doi: 10.1128/IAI.02284-14. Epub 2014 Sep 2.
Indwelling urinary catheters are commonly used in the management of hospitalized patients. Candida can adhere to the device surface and propagate as a biofilm. These Candida biofilm communities differ from free-floating Candida, exhibiting high tolerance to antifungal therapy. The significance of catheter-associated candiduria is often unclear, and treatment may be problematic considering the biofilm drug-resistant phenotype. Here we describe a rodent model for the study of urinary catheter-associated Candida albicans biofilm infection that mimics this common process in patients. In the setting of a functioning, indwelling urinary catheter in a rat, Candida proliferated as a biofilm on the device surface. Characteristic biofilm architecture was observed, including adherent, filamentous cells embedded in an extracellular matrix. Similar to what occurs in human patients, animals with this infection developed candiduria and pyuria. Infection progressed to cystitis, and a biofilmlike covering was observed over the bladder surface. Furthermore, large numbers of C. albicans cells were dispersed into the urine from either the catheter or bladder wall biofilm over the infection period. We successfully utilized the model to test the efficacy of antifungals, analyze transcriptional patterns, and examine the phenotype of a genetic mutant. The model should be useful for future investigations involving the pathogenesis, diagnosis, therapy, prevention, and drug resistance of Candida biofilms in the urinary tract.
留置导尿管常用于住院患者的护理。念珠菌可黏附于导尿管表面并形成生物膜进行繁殖。这些念珠菌生物膜群落与游离的念珠菌不同,对抗真菌治疗表现出高度耐受性。导尿管相关念珠菌尿的意义通常并不明确,考虑到生物膜的耐药表型,治疗可能会存在问题。在此,我们描述一种啮齿动物模型,用于研究导尿管相关白色念珠菌生物膜感染,该模型模拟了患者体内这一常见过程。在大鼠留置功能正常的导尿管的情况下,念珠菌在导尿管表面形成生物膜并增殖。观察到了典型的生物膜结构,包括嵌入细胞外基质中的黏附丝状细胞。与人类患者的情况类似,患有这种感染的动物出现了念珠菌尿和脓尿。感染发展为膀胱炎,在膀胱表面观察到类似生物膜的覆盖物。此外,在感染期间,大量白色念珠菌细胞从导尿管或膀胱壁生物膜中分散到尿液中。我们成功利用该模型测试了抗真菌药物的疗效,分析了转录模式,并研究了基因变异体的表型。该模型对于未来涉及尿路念珠菌生物膜的发病机制、诊断、治疗、预防和耐药性的研究应具有重要价值。