Utilization of N-acetylglucosamine by Streptococcus mutans and its regulation

变形链球菌对N-乙酰氨基葡萄糖的利用及其调控

基本信息

批准号：
8808938
负责人：
Lin Zeng
金额：
$ 11.25万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-12-01 至 2016-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8808938
关键词：
Acetylglucosamine Acids Amino Sugars Anabolism Bacillus subtilis Bacteria Biochemical Biogenesis Biological Assay Carbohydrates Carbon Catabolism Cell Wall Cells Communicable Diseases Communities Complex Consumption Coupled Data Deacetylase Deaminase Dental caries Development Diet Disease Progression Ecology Energy-Generating Resources Environment Environmental Impact Enzymes Equilibrium Escherichia coli Family Foundations Fructose Future Gene Expression Generations Genes Genetic Glucosamine Glucose Glutamine Goals Growth Homeostasis Human Individual Investigation Knowledge Lactobacillus Lead Mannose Metabolism Microbial Biofilms Modeling Molecular Molecular Biology Molecular Profiling Nitrogen Oral Oral cavity Oral health Organism Pathway interactions Peptidoglycan Periodontal Diseases Physiological Physiology Pilot Projects Planets Play Principal Investigator Process Production Property Protein S RNA Regulation Research Role Signal Transduction Site Source Streptococcus mutans Streptococcus pneumoniae Streptococcus pyogenes Taxon Virulence Virulence Factors Work base career cariogenic bacteria combat design differential expression fitness gene discovery improved lactic acid bacteria mRNA Stability microbial microbial community microorganism mutant new therapeutic target novel therapeutics oral bacteria oral biofilm pH Homeostasis pathogen promoter public health relevance response sugar tool tooth surface trait

项目摘要

DESCRIPTION (provided by applicant): Remarkably complex microbial communities colonize human oral cavity, and the composition and biochemical activities of the communities differ in healthy humans compared with individuals with dental caries or periodontal diseases. Interactions between oral biofilms and host environment warrant extensive study to better understand the initiation and progression of diseases. Carbohydrates in the human diet, and those provided by host secretions, host cells and microorganisms provide essential carbon and energy sources to many bacterial taxa that colonize human tooth surface. This is especially true for the lactic acid bacteria (LAB), which depend almost entirely on carbohydrates for energy and acid production. Glucosamine (GlcN) and N- acetylglucosamine (GlcNAc) are among the most abundant naturally-occurring sugars on the planet, and are catabolized by many bacterial species as a source of both carbon and nitrogen. In the absence of these amino sugars, bacteria also synthesize GlcN-6-P from fructose-6-P and glutamine for cell wall biogenesis. Despite the ubiquity of these amino sugars in the oral cavity, there have been very few studies regarding their utilization by the oral microbiota, and in particular by dental caries pathogens. Here, we present new data on the regulation and role in physiologic homeostasis of GlcN and GlcNAc utilization and biosynthesis in the major dental caries pathogen, Streptococcus mutans. Importantly, we show that the regulatory mechanisms governing the endogenous production of GlcN-6-P are different from paradigm models, such as Bacillus subtilis and Escherichia coli. Specifically, we have demonstrated that the genes responsible for GlcNAc catabolism encoding GlcNAc-6-P deacetylase (NagA) and GlcN-6-P deaminase (NagB), are negatively regulated by the GntR/HutC-family regulator NagR. While NagR-dependent regulation of nagAB is fairly common, we also discovered that the gene encoding the enzyme responsible for producing GlcN-6-P, GlmS, is also under direct control of NagR; a highly unusual finding since NagB catabolizes, but GlmS produces, GlcN-6-P. Moreover, the RNA-based pathways for control of glmS translational efficiency in E. coli or of mRNA stability in B. subtilis do not appear to be present in S. mutans. On the basis of these observations, we propose 1) to begin to dissect the molecular mechanisms maintaining the critical balance between NagB and GlmS activities and 2) to explore in more detail the physiologic and ecological benefits of the consumption of GlcNAc by S. mutans. The knowledge gained from these studies will provide critical information needed to understand amino sugar metabolism by S. mutans and related oral bacteria, which could lead to improved control of the pathogenic potential of the oral flora. In addition, many lactobacilli, group A streptococci, and Streptococcus pneumoniae, appear to share some key features in glmS regulation with S. mutans, so these investigations are of high relevance to a group of important human pathogens and commensals.

描述（由申请人证明）：鲜明的微生物群落在健康的人类中与龋齿或牙周扫描的人不同人类饮食植物的含量为许多碳牙齿的碳水化合物提供了必不可少的碳和能量来源。在没有果糖-6-P的Glcn-6-p的情况下，碳和氮的含量也是碳和谷氨酰胺，尽管已经存在口腔中的糖分，但它们是碳和氮的根源。很少有口服微生物群，尤其是龋齿病原体。与范式枯草和大肠杆菌不同。常规的Nagab是很普遍的，我们还发现了负责产生GLCN-6-P的酶，也是直接分解的GLCN-6-P。基于观察结果，核酸链球菌中的GLMS转化效率是枯草芽孢杆菌中的公证人。详细说明了S. mutans glcNAC的生态益处。许多乳酸杆菌，链球菌和链球菌似乎在GLMS调节中与S. Mutans共享一些关键特征，因此这些投资与一组重要的人类病原体和评论具有很高的相关性。