Microbial diversity, otitis media, and the pneumococcal transctiptome

微生物多样性、中耳炎和肺炎球菌转录组

基本信息

批准号：
8205562
负责人：
Melinda Mary Pettigrew
金额：
$ 24.83万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8205562
关键词：
3 year old Acute Age-Years Antibiotics Bacteria Biodiversity Bioinformatics Biological Response Modifier Therapy Biology Cell Line Child Childhood Clinical Complex Cross-Sectional Studies Data Detection Development Disease Epithelial Cells Genes Genome Haemophilus influenzae Health Human Incidence Infection Invaded Lead Meningitis Methodology Methods Minor Monitor NIH Program Announcements National Institute on Deafness and Other Communication Disorders Nose Otitis Media Outcome Pathway interactions Pattern Philadelphia Pneumococcal 7-Valent Conjugate Vaccine Pneumococcal Colonization Pneumonia Prevention strategy Preventive Probiotics Process Protocols documentation RNA RNA Sequences Relative (related person)Research Respiratory System Respiratory tract structure Risk Sampling Seasons Signal Transduction Site Stimulus Streptococcus pneumoniae Structure Structure of mucous membrane of nose Taxon Therapeutic Tissues Transcript Upper Respiratory Infections Upper respiratory tract Viral Respiratory Tract Infection Virulence cDNA Library design effective therapy insight member microbial microbial community novel novel strategies novel vaccines pathogen rRNA Genes resilience respiratory virus response theories treatment strategy vaccination strategy

项目摘要

DESCRIPTION (provided by applicant): Streptococcus pneumoniae asymptomatically colonizes the upper respiratory tract of healthy young children and is a leading cause of acute otitis media (OM). S. pneumoniae colonization is a critical step in the disease process and occurs in the context of a complex microbial community. Limited understanding of the relationships between bacterial colonization patterns and risk of OM has hindered the development of preventive and therapeutic strategies that maximize clinical outcomes and minimize disruptions to the protective commensal flora. Our proposed studies are in direct response to the NIDCD Program Announcement (PA-08-092) "Novel Approaches to Study Polymicrobial Diseases". We will analyze pre-existing data from a cross sectional study of 249 Philadelphia children 6 months to =3 years of age. Samples and data were collected during the 2009-10 winter respiratory virus season. High throughput 454 16S rRNA gene pyrosequencing will be used to characterize nasal microbial communities. RNA-sequencing (RNA-seq) on the Illumina Genome Analyzer 2 platform will be used to compare S. pneumoniae transcriptional profiles under a range of experimental conditions. Our specific aims are: 1) To characterize upper respiratory tract microbial community structure in a cross sectional sample of healthy children, children with acute OM, and children with other, primarily non-bacterial upper respiratory tract infections, which often precede the onset of acute OM and 2) To develop RNA- seq protocols and bioinformatics pipelines to study S. pneumoniae transcriptional profiles, alone and in the presence of key commensal species. These studies will identify members of the normal flora involved in the causal pathogenic pathway of S. pneumoniae colonization and acute OM. New methods will be developed to identify S. pneumoniae virulence genes uniquely expressed in polymicrobial settings. Over the long term these data will aid in the development of biotherapeutics such as probiotics and will also provide information relevant for the control of other bacterial pathogens that colonize the respiratory tract. PUBLIC HEALTH RELEVANCE: This research will elucidate relationships among upper respiratory tract microbial community composition and risk of pneumococcal colonization and otitis media. Results will facilitate development of prevention strategies for common bacterial pathogens.

描述（由申请人提供）：肺炎链球菌无疑地在健康幼儿的上呼吸道上定居，并且是急性中耳炎培养基（OM）的主要原因。肺炎链球菌定植是疾病过程中的关键一步，发生在复杂的微生物群落的背景下。对细菌定植模式和OM风险之间关系的了解有限，阻碍了预防和治疗策略的发展，这些策略最大程度地提高了临床结果并最大程度地减少了对保护性共生菌群的干扰。我们提出的研究直接回应了NIDCD计划公告（PA-08-092）“研究多虫病疾病的新方法”。我们将分析来自249名费城儿童6个月至= 3岁的费城儿童的横断面研究中存在的数据。在2009-10冬季呼吸道病毒季节收集了样品和数据。高吞吐量454 16S rRNA基因pyrosequencing将用于表征鼻微生物群落。 Illumina Genome Analyzer 2平台上的RNA测序（RNA-SEQ）将用于比较一系列实验条件下的肺炎链球菌转录曲线。 Our specific aims are: 1) To characterize upper respiratory tract microbial community structure in a cross sectional sample of healthy children, children with acute OM, and children with other, primarily non-bacterial upper respiratory tract infections, which often precede the onset of acute OM and 2) To develop RNA- seq protocols and bioinformatics pipelines to study S. pneumoniae transcriptional profiles, alone and in the presence of key commensal 物种。这些研究将确定与肺炎链球菌定植和急性OM的因果致病途径有关的正常植物群的成员。将开发新的方法来鉴定在多数型环境中唯一表达的肺炎链球菌毒力基因。从长远来看，这些数据将有助于开发益生菌等生物治疗剂，还将提供有关控制呼吸道的其他细菌病原体有关的信息。公共卫生相关性：这项研究将阐明上呼吸道微生物群落组成以及肺炎球菌定植和中耳炎的风险之间的关系。结果将有助于开发常见细菌病原体的预防策略。