CANDIDA ALBICANS-ASSOCIATED ORAL BIOFILMS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。念珠菌是人类的主要真菌病原体，是造成严重发病率和死亡率的原因。念珠菌病通常与在无生命或生物表面形成念珠菌生物膜有关，这种表型在粘膜和全身部位都有发现。据估计，基于生物膜的感染占所有人类微生物疾病的65%，通常对常规抗菌治疗难以治愈，并且是难治性感染的来源；因此，生物膜相关感染是一个重大的公共卫生问题。一些人工生物膜模型表明，成熟的念珠菌生物膜具有空间异质性和由细胞外基质包裹的微菌落组成的层状结构。然而，应该强调的是，临床生物膜很少，如果有的话，只由来自单一物种的细胞组成。事实上，口腔细菌和念珠菌之间的相互作用，如共聚集、共粘附、生长刺激或抑制，很可能在混合微生物生物膜的发展和维持中发挥重要作用。本研究的长期目标是了解口腔中白色念珠菌生物膜形成的生物学，并剖析生物膜群落中真菌和细菌物种之间的众多相互作用。具体来说，我们将1)确定念珠菌甘露蛋白是否对胞外多糖基质的生产很重要，2)研究由口腔细菌（链球菌）和白色念珠菌组成的混合物种生物膜的发展，以及3)鉴定和分析能够结合戈登链球菌的白色念珠菌糖蛋白。通过研究混合物种生物膜的形成并将这些知识应用于患者群体，我们将更好地了解许多基于生物膜的感染，包括假牙口炎和牙周病。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Candida species are the major fungal pathogen of humans and are responsible for significant morbidity and mortality. Candidiasis is often associated with the formation of Candida biofilms on the surface of inanimate or biological surfaces, and this phenotype is found at both mucosal and systemic sites. Biofilm-based infections are estimated to account for as much as 65% of all human microbial diseases, are frequently refractory to conventional antimicrobial therapy and are a source of recalcitrant infections; consequently, biofilm-associated infections represent a significant public health problem. Several artificial biofilm models have shown that mature Candida biofilms display spatial heterogeneity and a layered architecture consisting of extracellular matrix encased microcolonies. It should be emphasized, however, that clinical biofilms rarely, if ever, consist of only cells from a single species. Indeed interactions between oral bacteria and Candida such as coaggregation, coadhesion, growth stimulation or inhibition most likely play an important role in the development and maintenance of mixed-microbial biofilms. The long-term goal of this research is to understand the biology of Candida albicans biofilm formation in the oral cavity and to dissect the numerous interactions between fungal and bacterial species within a biofilm community. Specifically, we will 1) determine if Candida mannoproteins are important for exopolysaccharide matrix production, 2) study the development of a mixed-species biofilm consisting of oral bacteria (streptococci) and C. albicans, and 3) identify and analyze C. albicans glycoproteins capable of binding Streptococcus gordonii. By studying mixed-species biofilm formation and applying this knowledge to the patient population, we will gain a better understanding of many biofilm-based infections including denture stomatitis and periodontal disease.