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Peptide Mediated Cell-Cell Communications in Streptococcus mutans

变形链球菌中肽介导的细胞间通讯

基本信息

批准号：
9750517
负责人：
SASWATI BISWAS
金额：
$ 36.34万
依托单位：
UNIVERSITY OF KANSAS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2021-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9750517
关键词：
ATP-Binding Cassette Transporters Attention Binding C-terminal Cell Communication Cell Density Cell surface Cells Cleaved cell Communicable Diseases Communication Competence Complex Dental Plaque Dental caries Developed Countries Developing Countries Development Direct Repeats Disease Economic Burden Endocarditis Environment Evaluation Future Genes Genetic Glycine Goals Gram-Positive Bacteria In Vitro Integration Host Factors Knowledge Light Mediating Membrane Microbial Biofilms Molecular N-terminal Names Oral Organism Pathogenicity Pathway interactions Peptide Hydrolases Peptide Leader Sequences Peptide Signal Sequences Peptides Phenotype Pheromone Phosphorylation Phosphotransferases Physiological Processes Process Production Promoter Regions Protease Domain Regulation Signal Pathway Signal Transduction Signal Transduction Pathway Signaling Molecule Specificity Streptococcus Streptococcus mutans Structure Substrate Specificity Surface System Testing Translating Virulence analog bacteriocin base biological adaptation to stress density dental biofilm extracellular inorganic phosphate intercellular communication novel oral bacteria oral pathogen oral streptococci protein-histidine kinase quorum sensing response sensor stress tolerance tooth surface trait

项目摘要

ABSTRACT: Streptococcus mutans, an organism strongly associated with dental caries, utilizes a peptide-based cell density dependent signaling system known as quorum-sensing (QS). This signaling pathway is responsible for controlling major virulence traits such as bacteriocin production, biofilm formation, competence development, and stress tolerance. In S. mutans, one of the peptides responsible for cell-cell communication is competence- stimulating peptide (CSP). CSP acts as a signaling molecule to activate a two-component signal transduction pathway called ComDE. CSP is synthesized inside the cell as a pre-peptide of 46-residues long, in which the N-terminal 25-residue functions as a leader peptide. During secretion through a dedicated ABC transporter, the leader peptide is cleaved and the matured 21-residue long peptide (CSP21) is concentrated in the milieu. Our group was the first to identify the dedicated ABC transporter (NlmTE) necessary for CSP secretion. We also discovered that CSP21 is further processed by a highly conserved cell-surface associated protease, which we named SepM. We found that SepM cleaves CSP21 at the C-terminal end to create an 18-residue long active signaling molecule (CSP18). When extracellular concentration of CSP18 reaches a critical density, the ComD sensor kinase is activated by the peptide. The activated ComD then stimulates the ComE response regulator and a variety of genes necessary for the observed phenotypic changes are induced by the activated ComE. While the ComDE pathway is well studied at the phenotypic level, the molecular mechanisms by which CSP activates this signaling pathway have not been evaluated. In this application we propose to study the molecular mechanisms of CSP mediated cell-cell communication in S. mutans. Successful completion of this study could shed light on the molecular basis for inhibition of S. mutans biofilm formation through disruption of cell-cell communication.

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