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Role of Clp proteins in pathophysiology of Streptococcus mutans

Clp 蛋白在变形链球菌病理生理学中的作用

基本信息

批准号：
9912160
负责人：
Indranil Biswas
金额：
$ 34.43万
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：
2018
资助国家：
美国
起止时间：
2018-05-01 至 2022-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9912160
关键词：
ATP phosphohydrolase Adaptor Signaling Protein Adult Bacteria Bacterial Proteins Bacteriophages Biology C-terminal Cell Communication Cell division Cells Child ClpX protein Communities Competence Complex Cost of Illness Dental Plaque Dental caries Developed Countries Development Environment Escherichia coli Etiology Firmicutes Functional disorder Genes Goals Gram-Positive Bacteria Growth Heat-Shock Response Human Infective endocarditis Knowledge Lead Life Style Light Mass Spectrum Analysis Mediating Microbial Biofilms Molecular Molecular Chaperones N-terminal Nutrient Oral cavity Organism Pathogenicity Peptide Hydrolases Phosphorylation Play Production Protein Family Proteins Proteolysis Quality Control Regulation Regulatory Pathway Research Resistance Role Serine Protease Signal Transduction Streptococcus Streptococcus mutans Streptococcus pneumoniae Streptococcus pyogenes Stress Substrate Specificity System Temperature Virulence Virulence Factors bacterial community bacteriocin biological adaptation to stress environmental flux misfolded protein novel oral pathogen oral streptococci pathogen polymicrobial biofilm programs protein degradation response stress tolerance tooth surface trait

项目摘要

ABSTRACT Streptococcus mutans is considered the major etiological agent in dental caries. S. mutans is also an important agent of infective endocarditis. The organism colonizes the oral cavity by forming diverse, multispecies biofilms on the tooth surface, known as dental plaque. To survive in the hostile environment of the oral cavity, S. mutans has developed a robust stress tolerance response that depends on regulated proteolysis of damaged or misfolded proteins. Regulated proteolysis in bacteria is primarily controlled by the Clp (caseinolytic protease)-family of proteins that are composed of a small cytoplasmic serine protease, called ClpP, and various ATPases. ClpP associates with a partner ATPase to form a functional complex that specifically targets proteins for degradation or translocation. While ClpP degrades the damaged/misfolded protein, it is the ATPase component that determines the substrate specificity. In S. mutans, the Clp-system, in addition to stress tolerance responses, is also required for biofilm formation, bacteriocin production, competence development, cell-cell communications, and bacteriophage resistance. The Clp-system is well studied in Escherichia coli in which it encodes two major ATPases: ClpA and ClpX. While streptococci, including S. mutans, do not encode ClpA, they do encode ClpX. Furthermore, two other ATPases, ClpC and ClpE, which are absent in E. coli, are uniquely present in streptococci and other Fermicutes. Very little is known about the substrate specificity or the molecular mechanisms of protein degradation in streptococci in general. The first major goal of this project is to understand at the molecular level how ClpX recognizes and degrades substrate proteins and regulates various virulence traits. The second major aim is to understand the role of ClpE in stress response and pathophysiology in S. mutans since our studies indicate that ClpE is an important ATPase. We anticipate that completion of this project will lead to the identification of novel regulatory pathways and new players for protein quality control in S. mutans. Moreover, knowledge acquired from this project can also be extended to other important pathogens such as S. pneumoniae and S. pyogenes, and may lead to the identification of a novel regulatory pathway.

摘要