Candida-Bacteria Communication in Oral Biofilms

口腔生物膜中的念珠菌-细菌通讯

• 批准号: 8296366
• 负责人: HOWARD F JENKINSON
• 金额: $ 37.88万
• 依托单位: UNIVERSITY OF BRISTOL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-17 至 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8296366
• 关键词: A Mouse; Adherence; Adhesions; Bacteria; Bacterial Adhesins; Binding; Binding Sites; Biochemical; Biological Assay; Candida; Candida albicans; Cell surface; Cells; Clinical; Clinical Course of Disease; Communication; Communities; Community Developments; Complement; Complex; Data; Dental caries; Dentures; Deposition; Development; Diagnosis; Disease; Dissection; Filament; Gastrointestinal tract structure; Genes; Genome; Genomics; Gingiva; Growth; Human; Hyphae; I-antigen; Immune response; In Vitro; Infection; Infection Control; Intercept; Life Style; Maps; Measures; Mediating; Membrane Glycoproteins; Membrane Proteins; Metagenomics; Methods; Microbial Biofilms; Molecular; Mouth Diseases; Oral; Oral candidiasis; Oral cavity; Oral mucous membrane structure; Organism; Pathway interactions; Peptides; Periodontal Diseases; Periodontitis; Porphyromonas gingivalis; Process; Production; Property; Protein Family; Proteins; Public Health; Pulp Canals; RNA; Reaction; Research; Saccharomyces cerevisiae; Salivary; Signal Transduction; Signaling Molecule; Site; Site-Directed Mutagenesis; Source; Spectrum Analysis; Stomatitis; Streptococcus gordonii; Structure; Surface; System; Time; Tissues; Translating; VAI-2; Yeasts; adhesion process; base; cell type; computerized data processing; extracellular; fungus; human disease; in vivo; member; microbial; microorganism; mouse model; mutant; novel therapeutics; oral bacteria; oral biofilm; oral microbiome; oral streptococci; pathogen; polypeptide; prevent; receptor; response; single molecule; soft tissue; transcription factor

DESCRIPTION (provided by applicant): Polymicrobial communities are found on oral cavity surfaces as biofilms, embedded in a matrix of host salivary components and microbial extracellular products. These communities provide an infection source for diseases of the oral hard and soft tissues, and for systemic conditions. Communication reactions between the micro-organisms modulate the structure, composition and pathogenic potential of the communities. The oral streptococci are especially important in this respect because they are primary colonizers of oral cavity surfaces. Their deposition provides an attachment substrate for colonization by potentially pathogenic organisms such as Porphyromonas gingivalis and the fungus Candida albicans, which is the cause of most yeast infections in humans. Co-adhesion between C. albicans and oral bacteria is proposed to facilitate oral carriage and persistence of C. albicans, leading to disease conditions such as denture-induced stomatitis, oral candidiasis, periodontitis, and root canal infections. Studies have demonstrated that inter-microbial binding of Streptococcus gordonii and C. albicans involves complementary and co-operative adhesin-receptor molecules. Streptococcal cell surface-associated SspB adhesin, a member of the Antigen I/II protein family, binds C. albicans hyphal cell surface glycoprotein Als3p, resulting in close engagement of the surface molecules on the partner cell types. These adhesion processes drive the development and accumulation of mixed species biofilms that are morphologically, physiologically and pathogenically unique. The aims of this proposal are to: define the molecular mechanisms of C. albicans surface protein interactions with S. gordonii; characterize the signaling processes occurring in polymicrobial community development; determine the mechanisms of communication between C. albicans and P. gingivalis; investigate the impact of co-colonization in vivo. These aims, while covering a range of factors, will permit detailed analyses of molecular communication systems occurring between co-colonizing bacteria and fungi. Characterization of the mechanisms involved in co-colonization of denture materials, oral mucosa, and of sub-gingival tissues, will provide greater understanding of the factors relevant to polymicrobial-mediated oral disease initiation and progression at these sites. Potential targets for inhibition of co-adhesion and community development can thus be identified, and these may ultimately prove a means for the control of infection by C. albicans. PUBLIC HEALTH RELEVANCE: Fungi have emerged as major causes of human disease. Candida yeast infections are a serious threat to public health. This research devises new methods for controlling or preventing growth of Candida albicans in the mouth.

描述（由申请人提供）：在口腔表面上发现多数菌群作为生物膜，嵌入在宿主唾液成分和微生物细胞外产物的基质中。这些社区为口腔硬组织和系统条件的疾病提供了感染来源。微生物之间的通信反应调节了社区的结构，组成和致病潜力。口服链球菌在这方面尤其重要，因为它们是口腔表面的主要菌落。它们的沉积为潜在的致病生物（如牙龈卟啉单胞菌和真菌白色念珠菌）提供了固定的附着底物，这是人类大多数酵母菌感染的原因。提出了白色念珠菌与口腔细菌之间的共粘附，以促进白色念珠菌的口腔运输和持久性，从而导致疾病，例如牙齿诱发的口腔炎，口腔念珠菌病，牙周炎和根管感染。研究表明，高多氏链球菌和白色念珠菌的微生物间结合涉及互补和合作性粘附素受体分子。链球菌细胞表面相关SSPB粘附素是抗原I/II蛋白家族的成员，结合白色念珠菌菌丝菌丝细胞表面糖蛋白ALS3P，导致 表面分子在伴侣细胞类型上的紧密接合。这些粘附过程推动了混合物种生物膜的发展和积累，这些物种在形态，生理和病理上是独特的。该提议的目的是：定义白色念珠菌表面蛋白与Gordonii的分子机制；表征多数群体社区发展中发生的信号传导过程；确定白色念珠菌和牙龈疟原虫之间通信的机制；研究共殖化在体内的影响。这些目的在涵盖了一系列因素的同时，将允许对共殖化细菌和真菌之间发生的分子通信系统进行详细分析。对义齿材料，口服粘膜和亚生物组织共同殖民化的机制的表征将对这些地点的多数菌介导的口腔疾病起始和进展的因素有更深入的了解。因此，可以鉴定出抑制共粘附和社区发展的潜在靶标，这些目标最终可能证明是白色念珠菌控制感染的一种手段。 公共卫生相关性：真菌已成为人类疾病的主要原因。念珠菌酵母菌感染是对公共卫生的严重威胁。这项研究为控制或预防嘴中白色念珠菌的生长设计了新的方法。