Novel flow cell model to study oral mucosa-polymicrobial biofilm interactions

研究口腔粘膜-多种微生物生物膜相互作用的新型流动细胞模型

• 批准号: 7774194
• 负责人: Patricia Diaz
• 金额: $ 22.95万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2012-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7774194
• 关键词: 3-Dimensional; Accounting; Biological Models; Biological Preservation; Candida albicans; Candidiasis; Cell model; Cells; Characteristics; Communities; Cystic Fibrosis; Development; Device Designs; Disease; Disease susceptibility; Environment; Epithelial; Epithelium; Equilibrium; Etiology; Gastrointestinal tract structure; Gene Expression; Genes; Genitourinary system; Goals; Grant; Growth; Health; Human; In Vitro; Infection; Inflammatory; Integration Host Factors; Investigation; Lead; Maintenance; Microbial Biofilms; Modeling; Mucous Membrane; Oral; Oral cavity; Oral mucous membrane structure; Otitis; Pathogenesis; Peptides; Periodontal Diseases; Periodontitis; Physiology; Porphyromonas gingivalis; Prevention; Prevention strategy; Process; Production; Prosthesis; Publishing; Research; Role; Shapes; Sinusitis; Surface; System; Tissues; Tooth structure; Urogenital Diseases; analog; antimicrobial; base; connective tissue stroma; cytokine; in vitro Model; member; microbial; microbial community; microorganism; novel; novel therapeutics; oral biofilm; oral pathogen; public health relevance; trait

DESCRIPTION (provided by applicant): Microorganisms do not exist individually but are part of dynamic polymicrobial communities. Humans harbor polymicrobial communities that form biofilms in close proximity to different epithelial surfaces. In the oral cavity, biofilms mostly form on teeth or prosthetic devices and adjacent to the oral mucosa. In the susceptible host, oral biofilms containing species such as Candida albicans or Porphyromonas gingivalis constitute the primary etiology of infectious and inflammatory conditions such as candidiasis and periodontal disease. Therefore, the identification of strategies to eradicate oral biofilms or interfere with their development will aid in the treatment or prevention of such conditions. In order to develop such strategies we need to understand the factors that govern the formation of oral polymicrobial biofilm communities, including both the interactions occurring among community members and the role of the host in shaping biofilm characteristics. In this pilot grant we will characterize a novel in vitro model system where such questions can begin to be answered. The proposed model consists of a flow cell device designed to harbor a polymicrobial biofilm growing in the presence of an oral mucosa tissue analogue. In Aim A we will characterize the biofilm component of our model by determining the optimal experimental conditions for polymicrobial biofilm assembly by microbial consortia containing an oral pathogen (either P. gingivalis or C. albicans). In Aim B we will characterize the tissue component of our model (an oral mucosa 3-D analogue) by evaluating the production of cytokines and anti-microbial peptides in the presence and absence of biofilms under flow conditions. Finally, in Aim C we will examine the role of the adjacent epithelium on polymicrobial biofilm assembly and identify, via microarrays, genes differentially regulated by the host in C. albicans and P. gingivalis when forming part of a polymicrobial community. We envision that our new model will lead to the discovery of host factors that influence biofilm development in the oral environment. Such host factors can be examined further to understand their role in shaping polymicrobial biofilm growth in the oral cavity and oral biofilm-related disease susceptibility traits in humans. Furthermore, a better understanding of polymicrobial biofilm-host interactions will lead to the development of novel therapeutic strategies to interfere with biofilm formation.

描述（由申请人提供）：微生物不是单独存在的，而是动态多生物群落的一部分。人类藏有多数群落，形成与不同上皮表面相近的生物膜。在口腔中，生物膜主要在牙齿或假肢装置上形成，并与口腔粘膜相邻。在易感宿主中，含有白色念珠菌或卟啉念珠菌等物种的口服生物膜构成了传染病和炎症状况（例如念珠菌病和牙周疾病）的主要病因。因此，确定根除口腔生物膜或干扰其发展的策略将有助于治疗或预防这种情况。为了制定这种策略，我们需要了解控制口腔多生物生物膜群落形成的因素，包括社区成员之间发生的相互作用以及宿主在塑造生物膜特征中的作用。在这项飞行员赠款中，我们将描述一个新颖的体外模型系统，可以开始回答此类问题。所提出的模型由一个流动池装置组成，旨在在口服粘膜组织类似物的情况下携带生长的多生物生物膜。在目标A中，我们将通过确定含有口腔病原体（牙龈疟原虫或白色念珠菌）的微生物consortia来确定多成菌生物膜组装的最佳实验条件来表征我们模型的生物膜成分。在AIM B中，我们将通过评估在流动条件下存在和不存在生物膜的情况下评估细胞因子和抗微生物肽的产生，来表征我们模型的组织成分（口服粘膜3-D类似物）。最后，在AIM C中，我们将研究相邻上皮在多粒子生物膜组装中的作用，并通过微阵列鉴定由宿主在形成多肌液群落的一部分时，由宿主在白色念珠菌和牙龈孢子虫中差异调节。我们设想，我们的新模型将导致发现影响口腔环境中生物膜发展的宿主因素。可以进一步研究此类宿主因素，以了解它们在塑造口腔和口腔生物膜相关疾病易感性特征中塑造多生物生物膜生长中的作用。此外，更好地了解多肌生物膜宿主相互作用将导致发展新型治疗策略以干扰生物膜形成。