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Streptococcus mutans adaptation to oxidative stress by the Cid/Lrg system

变形链球菌通过 Cid/Lrg 系统适应氧化应激

基本信息

批准号：
9104859
负责人：
Sang-Joon Ahn
金额：
$ 36.96万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-01 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9104859
关键词：
Adolescent Adult Aerobic Affect Altruism Antibiotics Antitoxins Apoptosis Autolysis Bacteria Bacteriophages Biological Assay Carbon Cell Death Cell Survival Cells Child Chronic Disease Communities Competence Complex Confocal Microscopy Cytolysis Data Dental Plaque Dental caries Development Disease Elements Environment Equilibrium Feedback Gene Expression Genes Genetic Glucose Goals Green Fluorescent Proteins Growth Heat Stress Disorders Heat-Shock Response Homeostasis Human Hydrogen Peroxide Imaging technology In Vitro Infection Infective endocarditis Knowledge Life Style Link Measures Mediating Metabolic Pathway Metabolism Microbial Biofilms Microfluidics Modeling Molecular Mus Operon Oral Oral cavity Organism Oxidative Stress Oxygen Pathogenicity Pathway interactions Patient risk Pattern Phase Physiology Pit and Fissure Sealants Play Population Process Production Propidium Diiodide Protein Family Proteins Public Health Regulation Reporter Research Role Schools Series Signal Transduction Streptococcus gordonii Streptococcus mutans Stress System Toxin Virulence Water fluoridation base biological adaptation to stress cell injury coping mechanism disorder control fitness gene product improved in vivo insight member mutant new therapeutic target novel oral bacteria oral biofilm oral streptococci oxidation pathogen prevent programs public health relevance research study response stem stressor therapy development trait transcriptome sequencing treatment strategy

项目摘要

DESCRIPTION (provided by applicant): Streptococcus mutans is considered the principal etiological agent of human dental caries. The ability of the organism to survive a variety of harmful or stressful conditions and to emerge as numerically significant member of stable oral biofilm communities are essential elements for the persistence and cariogenicity of S. mutans. Such abilities are critical to understand how this organism colonizes and persists in specific niches, and are likely to interconnect with sophisticated adaptation mechanisms that allow the organism to maintain homeostasis within the dynamic oral microflora. This important aspect of S. mutans physiology will be pursued in this proposal by studying the homologous cidAB and lrgAB operons, recently identified as being highly balanced and coordinated during S. mutans growth in oxygen, as well as shown to play a significant role in a variety of key S. mutans virulence traits, including autolysis, biofilm formation, oxidative and heat stress, and genetic competence. More importantly, the cid and lrg operons were predicted to be analogous to bacteriophage-encoded holin/antiholin proteins (suggested to control the activity of bacteriophage-mediated cell death and lysis). The goals of this proposal are 1) to decipher the reciprocal regulatory circuits of regulatory feedback between the cid and lrg genes, 2) to identify and characterize the Cid/Lrg-mediated cellular and molecular mechanisms in S. mutans, and 3) to evaluate contribution of Cid and Lrg to the competitive fitness of S. mutans in-vitro and in-vivo. These objectives will advance our understanding of how S. mutans persists in biofilms that harbor a highly complex population of differentiated cells and dynamic metabolic processes, and represent a new avenue of bacterial programmed cell death research that will further fundamental knowledge relevant to other oral streptococci and Gram-positive organisms. Furthermore, establishing a link between biofilm development and cell death/lysis will provide another valuable insight into inhibition of the initiation or progression of dental caries and possibilities for improved therapy and disease control.