Molecular Basis for Ocular Surface Tropism in Conjunctivitis

结膜炎眼表向性的分子基础

• 批准号: 8670576
• 负责人: Michael S Gilmore
• 金额: $ 41万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-05-01 至 2018-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8670576
• 关键词: Accounting; Agglutinins; Antibiotic Resistance; Antibiotics; Antigens; Bacteria; Bacterial Adhesins; Bacterial Capsules; Bacterial conjunctivitis; Base Sequence; Binding; Binding Proteins; Biological; Campylobacter; Child; Childhood; Choline; Communicable Diseases; Conjunctivitis; Development; Disease; Disease Outbreaks; Enzymes; Epidemic; Epithelial Cells; Epitopes; Event; Eye; Eye Infections; Family; Genes; Genetic; Genetic Polymorphism; Genome; Genomics; Goals; Health Care Costs; Healthcare Systems; Homologous Gene; Infection; Infection prevention; Lead; Left; Lipoproteins; Maine; Measures; Mediating; Microbe; Molecular; Movement; Neuraminidase; Office Visits; Ophthalmology; Pathogenicity; Pathogenicity Island; Prevention; Preventive; Property; Proteins; Research; Respiratory Tract Infections; Site; Streptococcus; Streptococcus pneumoniae; Students; Surface; Testing; Therapeutic; Tropism; Vaccines; Virulence Factors; Work; base; capsule; college; comparative; comparative genomics; cost; cost effective; falls; follow-up; genome analysis; insertion/deletion mutation; medical specialties; novel; ocular surface; pressure; prevent; public health relevance; receptor; sound

DESCRIPTION (provided by applicant): The GOAL of this research is to establish a scientific basis for cost effective prevention of conjunctivitis. Bacterial conjunctivitis is a costly diseaseof children. There are > 4 million office visits in the US/yr. Among the most common infections of childhood, it is a leading cause for antibiotic use. Half of cases occur in children under 9 years, with an annual cost of over $500 million. Bacterial conjunctivitis is caused by unusual strains of unencapsulated S. pneumoniae that are largely incapable of causing disease at other body sites and are uniquely pathogenic for the eye. Falling between specialties of Ophthalmology and Infectious Diseases, these unusual microbes have largely gone unstudied. An especially large and well documented conjunctivitis outbreak, involving 698 students at Dartmouth College, and six months later, the same strain caused another outbreak among 101 young children and 120 family contacts in Maine. Vaccines target the primary virulence factor of S. pneumoniae - the capsule. However, the vaccine is completely ineffective in preventing conjunctivitis, a disease uniquely caused by strains that lack the capsule, leaving an unaddressed gap in coverage. If we understood the basis for the unusual tropism of unencapsulated pneumococci for the ocular surface - that is, the key factors allowing it to bind and colonize the eye - we could include epitopes of these factors in the vaccine already being used, thereby preventing a common disease of childhood, and saving hundreds of $ million in health care costs, and limiting a leading cause for treating children with antibiotics, which is now believed to be altering their flra as well as leading to antibiotic resistance. In preliminary studies, we undertook an expansive comparative genomics study to identify candidate factors that allow unencapsulated S. pneumoniae to bind to the ocular surface. This research proposes to follow up these leads by directly testing a prioritized list of the most strongly implicated adhesins and other colonization factors, for their ability to mediate attachment to the ocular surface. The proposed studies combine biological approaches, as well as state-of-the-art genomics approaches, to identify the most important colonization factors that lead to conjunctivitis.

描述（由申请人提供）：本研究的目的是为经济有效地预防结膜炎建立科学基础。细菌性结膜炎是一种代价高昂的儿童疾病。在美国，每年有1.04亿次办公室访问。在最常见的儿童感染中，它是使用抗生素的主要原因。一半的病例发生在9岁以下的儿童中，