Binding specificity and transcriptional regulation of antigen I/II adhesins in Streptococcus gordonii

戈登链球菌抗原 I/II 粘附素的结合特异性和转录调控

• 批准号: 10750592
• 负责人: Sarah Aitken
• 金额: $ 4.5万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-14 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10750592
• 关键词: Acetylation; Affect; Antigens; Bacterial Adhesins; Bacterial Attachment Site; Binding; Biology; Carbohydrates; Cell surface; Cells; Communicable Diseases; Communities; Community Developments; Complex; Custom; Data; Dental Pellicle; Dental Plaque; Dental caries; Dentistry; Dentists; Development; Disease; Electrophoretic Mobility Shift Assay; Environment; Family; Genetic Transcription; Glycoproteins; Growth; Health; Human; In Vitro; Knowledge; Lead; Life Style; Link; Lysine; Measures; Mediating; Microbe; Microbial Biofilms; Modeling; Molecular; Mucins; Mucous Membrane; Mutation; Oral; Oral cavity; Peptides; Periodontitis; Phosphotransferases; Play; Point Mutation; Polysaccharides; Protein Acetylation; Protein Family; Proteins; Public Health; Recombinants; Regulation; Regulatory Pathway; Reporting; Research; Role; Saliva; Scientist; Specificity; Streptococcus; Streptococcus gordonii; Structure; Surface; System; Testing; Training; Transcriptional Regulation; Vertebral column; bacterial genetics; career; clinical application; dental biofilm; experience; experimental study; gene repression; genetic approach; improved; in vivo; microbial; microbial community; novel therapeutics; oral commensal; oral infection; polymicrobial biofilm; promoter; response; salivary mucins; sensor; sensor histidine kinase; surface coating; tooth surface

Project Summary/Abstract Bacterial expression of cell surface-associated adhesin proteins facilitates the formation of biofilms. Dental plaque is a polymicrobial biofilm of the human mouth that contributes to oral infectious diseases. Formation of this dental biofilm is initiated by pioneer colonization, whereby Streptococcus species use adhesin proteins to attach to the saliva-coated tooth surface. Among the many adhesins expressed by Streptococci, the antigen type I/II (AgI/II) adhesin family is widely conserved and has been shown to mediate interactions with several host molecules and other oral microbes. This proposal uses Streptococcus gordonii as a model to investigate the role of AgI/II adhesins in host surface attachment and biofilm development. S. gordonii is an oral commensal that expresses two AgI/II adhesins: SspA and SspB (SspA/B). Evidence shows that SspA/B is necessary for attachment to salivary mucin 5B (MUC5B)-coated surfaces. Proposed experiments will investigate binding between SspA/B proteins and MUC5B glycans. The variable (V) regions of SspA and SspB are expected to differentially bind the O-glycans decorating the MUC5B peptide backbone, contributing to initial attachment. SspA/B expression decreases, however, as the biofilm matures, suggesting that transcriptional regulation of sspA/B is complex. Data suggests that after initial surface attachment, protein acetylation regulates sspAB expression via the two-component system BfrAB. Therefore, genetic approaches are proposed to investigate the role of protein acetylation in sspA/B gene transcription. Overall, these studies will show that S. gordonii AgI/II adhesins mediate binding to MUC5B and are transcriptionally regulated by acetylation of the BfrB sensor kinase. Findings may be broadly applicable to streptococcal AgI/II adhesins and may suggest new mechanisms to control microbial community development in health and in streptococcal disease.

项目总结/摘要 细胞表面相关粘附素蛋白的细菌表达促进生物膜的形成。牙科 牙菌斑是人类口腔的多微生物生物膜，其导致口腔感染性疾病。形成 这种牙齿生物膜是由先锋定殖启动的，其中链球菌物种使用粘附素蛋白， 附着在唾液覆盖的牙齿表面。在链球菌表达的许多粘附素中，抗原类型 I/II（AgI/II）粘附素家族是一个高度保守的家族，它与多种宿主细胞相互作用 分子和其他口腔微生物。本研究以格氏链球菌为模型， AgI/II粘附素在宿主表面粘附和生物膜形成中的作用。S. gordonii是一种口服避孕药， 表达两种AgI/II粘附素：SspA和SspB（SspA/B）。有证据表明，SspA/B是必要的， 附着于唾液粘蛋白5 B（MUC 5 B）包被的表面。拟议的实验将研究结合 SspA/B蛋白和MUC 5 B聚糖之间的差异。预期SspA和SspB的可变（V）区 差异结合修饰MUC 5 B肽骨架的0-聚糖，有助于初始附着。 然而，随着生物膜的成熟，SspA/B的表达减少，这表明SspA/B的转录调控可能与生物膜的生长有关。 sspA/B是复杂的。数据表明，在最初的表面附着后，蛋白质乙酰化调节sspAB， 通过双组分系统BfrAB表达。因此，提出了遗传方法来研究 蛋白质乙酰化在sspA/B基因转录中的作用。总体而言，这些研究将表明S.戈登氏AgI/II 粘附素介导与MUC 5 B的结合，并通过BfrB传感器激酶的乙酰化进行转录调节。 研究结果可能广泛适用于链球菌AgI/II粘附素，并可能提出新的机制， 控制健康和链球菌疾病中的微生物群落发展。