Identifying targets for diagnosing oral candidiasis

描述（由申请人提供）：念珠菌是健康受试者口腔、粘膜表面和胃肠道的正常共生体，但在宿主的生理和免疫变化下，可引起各种疾病，从组织和皮肤的粘膜感染到危及生命的全身性疾病。白色念珠菌是口腔念珠菌病的主要真菌病原体，常见于免疫抑制患者、糖尿病患者、服用抗生素的患者、婴儿、吸烟者和hiv阳性患者。然而，口腔念珠菌病的诊断是复杂的，因为目前的诊断方法耗时，可能无法区分不同的念珠菌种类，最重要的是，无法区分无症状念珠菌携带者和口腔念珠菌病患者；这可能导致误诊，导致发病率增加，费用增加和抗真菌药物的过度处方。该I期申请的目标是鉴定在口腔感染期间仅表达的白色念珠菌基因生物标志物。利用一种独特的口腔念珠菌病小鼠模型，我们将使用抑制减法杂交和全局转录谱来鉴定和比较口腔组织感染期间表达的白色念珠菌基因和消化道定植期间表达的基因。潜在的疾病生物标志物将使用候选方法进行验证并确定优先顺序。本工作的最终目标是将I期发现的疾病生物标志物发展为快速、敏感和特异性的PCR诊断方法，以识别感染念珠菌的患者，并将定殖在健康宿主中的念珠菌与口腔念珠菌病患者区分开来。由于念珠菌是口腔最重要的真菌病原体，使用新的疾病生物标志物快速准确地诊断口腔念珠菌病将显著改善口腔健康。

DESCRIPTION (provided by applicant): Candida species are normal commensals of the oral cavity, mucosal surfaces, and gastrointestinal tract in healthy subjects but under physiological and immunological changes in the host, can cause a variety of maladies ranging from mucosal infections of the tissues and skin to life threatening systemic disease. Candida albicans is the major fungal pathogen responsible for oral candidiasis which commonly occurs in immunosuppressed patients, diabetics, patients taking antibiotics, infants, smokers and HIV-positive patients. Diagnosis of oral candidiasis is complicated, however, by the fact that current diagnostic methodologies are time consuming, may not differentiate between the different Candida species, and most importantly, do not distinguish between asymptomatic Candida carriers and patients with oral candidiasis; this can result in misdiagnosis leading to increased morbidity, increased expense and the over-prescription of antifungals. The goals of this Phase I application are to identify C. albicans gene biomarkers which are expressed solely during oral infection. Using a unique gnotobiotic mouse model of oral candidiasis, we will use suppressive subtracted hybridization and global transcription profiling to identify and compare C. albicans genes expressed during oral tissue infection to genes expressed during alimentary tract colonization. Potential disease biomarkers will be verified using candidate approaches and prioritized. The ultimate goal of this work is to develop the disease biomarkers discovered in Phase I, into a quick, sensitive and specific PCR diagnostic assay to identify patients infected with Candida species and to differentiate Candida colonizing the healthy host from patients with oral candidiasis. Since Candida species are the most important fungal pathogen of the oral cavity, the rapid and accurate diagnosis of oral candidiasis using novel disease biomarkers will significantly improve oral health.