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：
9220806
负责人：
Sang-Joon Ahn
金额：
$ 36.93万
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/9220806
关键词：
Adolescent Adult Aerobic Affect Altruism Antibiotics Antitoxins Apoptosis Autolysis Bacteria Bacteriophages Biological Assay Carbon Cell Death Cell Differentiation process Cell Survival Cells Child Chronic Disease Communities Competence Complex Confocal Microscopy Cytolysis Data Dental Plaque Dental caries Development Diatoms Disease Elements Environment Etiology Feedback Gene Expression Genes Genetic Genetic Transcription 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 Phenotype Physiology Pit and Fissure Sealants Play Population Prevention strategy 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 dental agent disorder control experimental study 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 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.

描述（由应用提供）：链球菌突变被认为是人类龋齿的主要病因学药。生物体生存各种有害或压力条件的能力，并成为稳定口腔生物膜群落中具有数值意义的成员的能力，这是S. mutans的持久性和性核心性的重要因素。这样的能力对于了解该生物如何在特定的小境中定居和持续存在至关重要，并且很可能与复杂的适应机制相互联系，从而使组织能够在动态口腔微生物中维持稳态。该提案将通过研究同源的cidab和lrgab操纵子来追求S. mutans生理的这一重要方面，最近被确定为在氧气中的S. mutans生长过程中具有高度平衡和协调，并且显示出在各种关键的S. mutans病毒性质中发挥重要作用，包括自动化，生物纤维形成，氧化和氧化，氧化和氧化，氧化和概念，并具有氧化，氧化和氧化能力，氧化和氧化。更重要的是，预测CID和LRG操纵子类似于细菌构造的霍林/抗蛋白蛋白（建议控制细菌介导的细胞死亡和裂解的活性）。该提案的目标是1）破译CID和LRG基因之间调节反馈的相互监管回路，2）确定并表征CID/LRG介导的链球菌中的细胞和分子机制，以及3）评估CID和LRG对暴力链球菌在体外和体内的竞争适应性的贡献。这些目标将促进我们对生物膜中如何持续存在的生物膜中的理解，这些生物膜具有高度复杂的分化细胞和动态代谢过程，并代表了细菌编程的细胞死亡研究的新途径，该研究将进一步与其他口腔链球菌和革兰氏阳性组织相关的基本知识。此外，建立生物膜发育与细胞死亡/裂解之间的联系将为抑制牙齿龋齿的抑制或进展提供另一个有价值的见解，并可能改善治疗和疾病控制。