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/文摘