Studies of YlxM of Streptococcus mutans, a newly identified component of the Sign

变形链球菌 YlxM 的研究，这是一种新发现的标志成分

• 批准号: 8596048
• 负责人: Matthew Lawrence Williams
• 金额: $ 3.84万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8596048
• 关键词: Acids; Adolescent; Adult; Affect; Autolysin; Bacteria; Bacterial Adhesins; Bacterial Proteins; Binding; Biological; Biological Process; Catalysis; Cell membrane; Cell physiology; Cells; Child; Chronic Disease; Communicable Diseases; Competence; Complex; Data; Defect; Dental Enamel; Dental caries; Developed Countries; Dietary Carbohydrates; Drug Efflux; Elements; Environment; Evolution; Expenditure; Fellowship; Fusobacteria; GTP Binding; Genes; Gnotobiotic; Goals; Gram-Negative Bacteria; Gram-Positive Bacteria; Growth; Guanosine; Guanosine Triphosphate; Health Expenditures; Healthcare; Homologous Gene; Human; Hydrolysis; Lactic acid; Life; Light; Link; Membrane; Membrane Proteins; Modeling; Mus; Mycoplasma; National Institute of Dental and Craniofacial Research; Oral health; Organelles; Organism; Oxidative Stress; Pathogenesis; Pathogenicity; Pathway interactions; Peptide Signal Sequences; Peptides; Play; Population; Process; Production; Protein translocation; Proteins; RNA; Rattus; Receptor Signaling; Reporting; Research; Research Personnel; Research Support; Ribosomes; Role; Signal Recognition Particle; Signal Transduction; Specific qualifier value; Streptococcus mutans; Stress; Students; System; Testing; Toxin; Translations; Virulence; Virulence Factors; base; capsule; demineralization; efflux pump; environmental stressor; global health; interest; membrane biogenesis; microorganism; mutant; novel; oral bacteria; oral pathogen; pathogen; pathogenic bacteria; polypeptide; public health relevance; quorum sensing; receptor binding; resilience; translocase; uptake

DESCRIPTION (provided by applicant): Membranes serve to delineate the boundaries of living cells and proteins incorporated into membranes help to define their biological functions. The relevance of bacterial membrane proteins is exemplified by the fact that nearly a third of all bacterial proteins produced are membrane-associated or secreted. Streptococcus mutans is a cariogenic oral pathogen whose virulence is determined in large part by its membrane composition. Human dental caries is a ubiquitous infectious disease that represents 5-10% of healthcare expenditures in industrialized nations. The Signal Recognition Particle (SRP) pathway of Streptococcus mutans is known to play an important role in its membrane biogenesis and pathogenesis. A further understanding of this pathway is necessary to understand the basic underlying machinery by which S. mutans virulence factors get into or through the cytoplasmic membrane. S. mutans SRP mutants demonstrate growth defects, are unable to contend with acid, osmotic, or oxidative stress, and demonstrate significantly decreased cariogenicity in a murine model. The SRP pathway is a co-translational protein translocation system that is conserved in all living cells. In bacteria three conserved components are recognized: Ffh, a protein with GTP hydrolysis (GTPase) activity that binds nascent polypeptides; FtsY, a membrane bound receptor that binds Ffh and helps target nascent peptides to the translocon channel; and a small cytoplasmic RNA (scRNA) that is involved in the stability of Ffh-FtsY and catalysis of GTPase activity. This proposal will investigate YlxM, a previously uncharacterized protein whose gene is found immediately upstream of ffh in S. mutans and other Gram- positive and some Gram-negative organisms. Based on preliminary data presented in this application YlxM is hypothesized to represent an additional component of the S. mutans SRP pathway. Three aims are proposed: 1) To confirm and characterize the interaction of YlxM with Ffh; 2) To confirm and characterize the interaction of YlxM with the scRNA; and 3) Evaluate the influence of YlxM on the function of SRP pathway components. This research supports the NIDCR goal to investigate cariogenic organisms to identify genes and pathways that contribute to the decay process. Additionally this research represents the basis of a doctoral dissertation project. Hence, this fellowship application will assist in trainin a student with an interest in oral health research to become an independent investigator.

描述（由申请人提供）：膜用于描绘活细胞的边界，并且掺入膜中的蛋白质有助于定义其生物学功能。细菌膜蛋白的相关性通过以下事实来例证：产生的所有细菌蛋白中的近三分之一是膜相关的或分泌的。变形链球菌是一种致龋性口腔病原体，其毒力在很大程度上由其膜组成决定。人类龋齿是一种普遍存在的传染病，占工业化国家医疗保健支出的5-10%。变形链球菌的信号识别颗粒（SRP）通路在其膜生物发生和致病过程中起重要作用。进一步了解这一途径是必要的，以了解基本的潜在机制，S。变形菌毒力因子进入或穿过细胞质膜。S.在鼠模型中，变形菌SRP突变体表现出生长缺陷，不能对抗酸、渗透压或氧化应激，并表现出显著降低的致龋性。SRP途径是在所有活细胞中保守的共翻译蛋白质易位系统。在细菌中，三种保守的组分被识别：Ffh，具有GTP水解（GTdR）活性的蛋白质，其结合新生多肽; FtsY，膜结合受体，其结合Ffh并帮助将新生肽靶向至易位子通道;以及小细胞质RNA（scRNA），其参与Ffh-FtsY的稳定性和GTdR活性的催化。该提案将研究YlxM，一种以前未表征的蛋白质，其基因在S.变形菌和其它革兰氏阳性和一些革兰氏阴性生物。基于本申请中提供的初步数据，假设YlxM代表S. mutans SRP途径。提出了三个目标：1）确认和表征YlxM与Ffh的相互作用; 2）确认和表征YlxM与scRNA的相互作用;和3）评估YlxM对SRP途径组分的功能的影响。这项研究支持了NIDCR的目标，即调查致龋生物，以确定有助于衰变过程的基因和途径。此外，这项研究是博士论文项目的基础。因此，这项奖学金申请将有助于培训一名对口腔健康研究感兴趣的学生成为一名独立的研究者。