Analysis Of Group A Streptococcus-Saliva Interaction

A 族链球菌-唾液相互作用的分析

• 批准号: 7436313
• 负责人: SAMUEL A SHELBURNE
• 金额: $ 0.35万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-08-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7436313
• 关键词: Acute Pharyngitis; Adhesions; Amino Acids; Animal Model; Area; Asses; Cell surface; Characteristics; Childhood; Clinical; Complex; Custom; Environment; Extracellular Protein; Flow Cytometry; Gene Chips; Gene Expression; Gene Expression Profile; Genes; Genome; Goals; Growth; Heart Diseases; Host Defense; Human; Immune system; Impetigo; In Vitro; Infection; Insertional Mutagenesis; Investigation; Ions; Knowledge; Laboratories; Lead; Measures; Metabolism; Methods; Microarray Analysis; Molecular; Morbidity - disease rate; Necrotizing fasciitis; Oral cavity; Organism; Oropharyngeal; Pathogenesis; Patients; Peptide Signal Sequences; Pharyngeal structure; Pharyngitis; Polymerase Chain Reaction; Post-Streptococcal Glomerulonephritis; Preventive; Proteins; Range; Research; Reverse Transcription; Rheumatic Fever; Saliva; Standards of Weights and Measures; Streptococcus; Streptococcus pyogenes; Techniques; Therapeutic; Time; Toxic Shock Syndrome; Transcript; Vaccines; Western Blotting; cost; design; extracellular; in vivo; microorganism; mortality; mutant; pathogen; prevent; vector transmission

DESCRIPTION (provided by applicant): This study is designed to examine the interaction of group A Streptococcus (GAS) with saliva. The key goal of the proposed research is to initiate the molecular investigation of a crucial area of GAS pathogenesis. Importantly, GAS-saliva interaction has been the subject of little inquiry despite knowing for 60 years that saliva is a major vector for the transmission of GAS from patients who have pharyngitis. Also, given that saliva coats the posterior pharynx, there is constant interplay between saliva and GAS during pharyngeal infection. Knowledge of how GAS responds to saliva will augment our understanding of how GAS infects the human oropharynx and spreads from patients with pharyngitis. Aim 1: To asses GAS global gene expression when cultivated in human saliva. For this aim, we will use Affymetrix custom-designed expression microarrays to analyze the GAS transcriptome during growth in human saliva. We will optimize use of the expression microarray analysis by futher investigation of GAS genes that are highly expressed during growth in saliva or that are upregulated during growth in saliva compared to growth in standard laboratory media. We will focus our inquiry on genes encoding extracellular proteins, as these are most likely to participate in host-pathogen interaction. Aim 2: To determine whether targeted GAS extracellular protein-encoding genes highly expressed or upregulated during in vitro GAS-saliva interaction are expressed similarly in vivo in humans with pharyngitis. Aim 3: To establish whether specific GAS extracellular proteins are produced during growth in human saliva. Aim 4: To determine whether inactivation of particular GAS extracellular protein-encoding genes identified by successful completion of Specific Aims 1-3 results in altered growth in human saliva. As GAS-saliva interaction has been minimally investigated, many of the genes examined in the proposed research are likely to be part of the 40% of the GAS genome encoding proteins of unknown function. This project seeks to contribute to fundamental understanding of GAS pathogenesis in the human oropharynx which may stimulate new avenues of investigation for therapeutic or preventive measures for this common pathogen. GAS pharyngitis costs an estimated $15 billion/year in the US alone, and as the instigator of rheumatic fever, GAS remains, worldwide, the leading cause of preventable pediatric heart disease.

描述（由申请人提供）：本研究旨在检查A组链球菌（气）与唾液的相互作用。拟议研究的关键目的是启动对气体发病机理至关重要区域的分子研究。重要的是，尽管60年来知道唾液是从患有咽炎的患者传播气体的主要媒介，但气体 - 萨利瓦相互作用几乎没有询问。同样，鉴于唾液涂层后咽后，咽部感染过程中唾液和气体之间存在恒定的相互作用。了解天然气对唾液的反应将增强我们对气体如何感染人类口咽的理解，并从患有咽炎的患者中传播。目的1：在人类唾液中种植时，要使气体全球基因表达。为此，我们将使用Affymetrix自定义设计的表达微阵列来分析人类唾液生长过程中的气体转录组。与标准实验室培养基的增长相比，我们将通过对唾液生长期间高度表达的气体基因的持续研究来优化表达微阵列分析的使用。我们将把询问集中在编码细胞外蛋白的基因上，因为这些基因最有可能参与宿主 - 病原体相互作用。目标2：确定靶向气体外蛋白质编码基因在体外气 - - 盐相互作用期间高表达或上调的基因是否在人体中类似地表达了咽炎的体内。目标3：确定在人类唾液生长过程中是否产生特定的气体外蛋白。目标4：确定通过成功完成特定目标1-3鉴定的特定气体外蛋白编码基因的灭活是否会导致人类唾液的生长改变。由于已经对气体 - 六面的相互作用进行了最小的研究，因此在拟议的研究中检查的许多基因可能是编码未知功能的蛋白质的40％的气体基因组中的一部分。该项目旨在为人类口咽中气体发病机理的基本理解做出贡献，这可能会激发该常见病原体治疗或预防措施的新研究途径。天然气咽炎仅在美国就估计每年150亿美元，并且作为风湿热，天然气仍然是全球的煽动者，是可预防的小儿心脏病的主要原因。