Bacterial Evasion of Innate Defenses at the Ocular Surface

细菌逃避眼表的先天防御

• 批准号: 10011825
• 负责人: Daria N Van Tyne
• 金额: $ 23.61万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10011825
• 关键词: Achievement; Affect; Anti-Bacterial Agents; Antibiotic Resistance; Antibiotics; Antimicrobial Resistance; Award; Bacteria; Bacterial Eye Infections; Bacterial Genes; Biology; Clinical; Clinical Research; Collaborations; Collection; Communicable Diseases; Communication; Comparative Genomic Analysis; Complement; Cornea; Corneal Diseases; Corneal Ulcer; Development; Disease; Drug resistance; Ear; Environment; Epithelial Cells; Escherichia coli; Extended-spectrum β-lactamase; Eye; Eye Infections; Film; Funding; Genes; Genetic; Genomic approach; Goals; Gram-Negative Bacteria; Healthcare; Host Defense; Human; Human Activities; Immune; Immunobiology; Immunologics; In Vitro; Infection; Institutes; Institution; Investigation; Keratitis; Klebsiella pneumoniae; Leadership; Mediating; Mentors; Microbe; Microbial Drug Resistance; Microbiology; Minor; Molecular; Motivation; Multi-Drug Resistance; Multiple Bacterial Drug Resistance; Mutation; Ophthalmology; Organism; Pathogenesis; Pathway interactions; Phagocytes; Phagocytosis; Phase; Phenotype; Population; Process; Pseudomonas Infections; Pseudomonas aeruginosa; Public Health; Research; Research Personnel; Research Proposals; Research Training; Resistance; Resources; Serratia; Serum; Site; Testing; Therapeutic; Training; Vision; Work; career; career development; cell motility; clinical practice; combat; comparative genomics; corneal epithelial cell adhesion; experience; host-microbe interactions; improved; insight; microbial; microbial genomics; mucoid; neutrophil; novel; novel therapeutic intervention; ocular surface; pathogen; pathogenic bacteria; recruit; resistance gene; resistance mechanism; resistant strain; skills; therapeutic development; tissue tropism; tool; trait; treatment strategy; wound healing

Project Summary/Abstract Bacterial keratitis is a sight-threatening condition often caused by Gram-negative organisms. A recent study of keratitis caused by multidrug-resistant E. coli highlights the need to better understand how these bacteria adapt to cause disease on the ocular surface. The long-term objective of this proposal is to build a greater understanding of the bacterial factors that contribute to corneal disease, and to target key processes for therapeutic development. The near-term objective is to provide the candidate with additional training in corneal immunobiology and host-pathogen interactions through a one-year mentored training experience, which will serve as a springboard to launch an independent research career developing new treatment strategies for drug-resistant microbial infections of the ocular surface. The candidate has abundant experience in molecular microbiology and microbial genomics, and now seeks additional training in a new but related field before launching an independent research career. As the candidate's mentor describes, the candidate is an outstanding trainee with abundant potential and a broad set of skills and experiences that she now seeks to apply to the to the development of new treatments for infections of the eye that are confounded by antimicrobial resistance. The candidate has an outstanding track record of achievement in research, training and leadership. She has successfully competed for independent research funding, and she is creative, hard working, highly collaborative, and has strong communication skills. In the mentor's own words, Dr. Van Tyne “is an ideal candidate for a K99/R00 award.” The environment is well suited to the candidate's proposal. The Mass Eye and Ear combines world- class clinical practice and research excellence in a single institution. The Department of Ophthalmology is a high quality research environment with many investigators that are capable of productive collaboration with the candidate, and has a demonstrated track record of providing successful training and career development. The Infectious Disease Institute maintains a clinical strain collection that will be a unique resource leveraged by this project. The Gilmore lab is generously funded and can offer additional support and resources to the candidate's project. The research plan put forth by the candidate consists of three aims. Aim 1 will investigate E. coli survival in human tears and human serum. Aim 2 will answer the question: how does mucoidy alter the host- microbe dynamic? Aim 3 will utilize comparative genomics approaches to compare large populations of Gram- negative ocular bacterial pathogens with bacteria from other infection sites, in order to identify genetic features that contribute to tissue tropism.

项目摘要/摘要 细菌性角膜炎是一种危害视力疾病，通常是由革兰氏阴性生物引起的。最近 由多药耐药大肠杆菌引起的角膜炎的研究强调了更好地了解这些的需求 细菌适应在眼表上引起疾病。该提议的长期目标是建立 对有助于角膜疾病的细菌因素有更深入的了解，并针对关键过程 用于热发育。近期目标是为候选人提供额外的培训 通过一年的培训经验，角膜免疫生物学和宿主 - 病原体相互作用， 它将作为开展独立研究职业开发新治疗的跳板 眼表面耐药微生物感染的策略。 候选人在分子微生物学和微生物基因组学方面具有丰富的经验，现在 在启动独立研究职业之前，在新的但相关的领域寻求额外的培训。作为 候选人的心理描述，候选人是一名出色的实习生，具有丰富的潜力，广泛 她现在寻求申请开发新治疗的技能和经验 被抗菌抗性混淆的眼睛感染。候选人有一条出色的曲目 研究，培训和领导力的成就记录。她成功地争夺了独立 研究资金，她是富有创造力，努力工作，高度协作的，并且具有较强的沟通能力。 用导师自己的话说，范·泰恩（Van Tyne）博士“是K99/R00奖的理想候选人。” 环境非常适合候选人的提议。大量的眼睛和耳朵结合了世界 - 单个机构的班级临床实践和研究卓越。眼科系是 许多能够与产品合作的调查员的高质量研究环境 候选人，并具有提供成功培训和职业发展的往绩。 传染病研究所维持临床应变收集，这将是由此利用的独特资源 项目。吉尔莫尔实验室是慷慨资助的，可以为 候选人的项目。 候选人制定的研究计划包括三个目标。 AIM 1将调查大肠杆菌 在人眼泪和人类血清中的生存。 AIM 2将回答以下问题：粘液中的粘液如何改变宿主 - 微生物动态？ AIM 3将利用比较基因组学方法来比较大量的革兰氏集种群 为了鉴定遗传特征，带有来自其他感染部位的细菌的阴性眼细菌病原体 这有助于组织偏向主义。