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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

基本信息

批准号：
8036979
负责人：
Patricia Diaz
金额：
$ 19.02万
依托单位：
UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-01 至 2013-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8036979
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 trait

项目摘要

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）：微生物不单独存在，而是动态多微生物群落的一部分。人类体内含有多微生物群落，它们在不同上皮表面附近形成生物膜。在口腔中，生物膜主要形成在牙齿或假体装置上并邻近口腔粘膜。在易感宿主中，含有诸如白色念珠菌或牙龈卟啉单胞菌的物种的口腔生物膜构成感染性和炎性病症诸如念珠菌病和牙周病的主要病因。因此，确定消除口腔生物膜或干扰其发展的策略将有助于治疗或预防此类病症。为了制定这样的战略，我们需要了解的因素，管理口腔多微生物生物膜群落的形成，包括社区成员之间发生的相互作用和主机在塑造生物膜特性的作用。在这个试点补助金，我们将描述一种新的体外模型系统，这些问题可以开始得到回答。所提出的模型由流动池装置组成，该装置旨在容纳在口腔粘膜组织类似物存在下生长的多微生物生物膜。在目标A中，我们将通过确定含有口腔病原体（牙龈卟啉单胞菌或C.白色念珠菌）。在目的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细胞因子和抗微生物肽的产生来表征我们的模型（口腔粘膜3-D模拟物）的组织组分。最后，在目标C中，我们将研究相邻上皮细胞对多微生物生物膜组装的作用，并通过微阵列鉴定C中宿主差异调节的基因。白色念珠菌和牙龈卟啉单胞菌时，形成多微生物群落的一部分。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育的宿主因素。可以进一步检查这些宿主因素，以了解它们在形成口腔中的多微生物生物膜生长和人类口腔生物膜相关疾病易感性特征中的作用。此外，更好地了解多微生物生物膜-宿主相互作用将导致开发新的治疗策略来干扰生物膜形成。