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.

项目总结/摘要 细菌性角膜炎是一种威胁视力的疾病，通常由革兰氏阴性菌引起。最近的一 多重耐药大肠杆菌致角膜炎研究大肠杆菌强调需要更好地了解这些 细菌适应于引起眼表疾病。这项建议的长远目标是建立一个 更好地了解导致角膜疾病的细菌因素，并针对关键过程 用于治疗发展。近期目标是为候选人提供以下方面的额外培训： 角膜免疫生物学和宿主-病原体相互作用通过一年的指导培训经验， 这将作为一个跳板，启动一个独立的研究生涯，开发新的治疗方法， 针对眼表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有丰富的经验，现在 在开始独立研究生涯之前，寻求新但相关领域的额外培训。为 应聘者导师介绍，应聘者是一名优秀的实习生，具有丰富的潜力和广泛的背景 她现在寻求将这些技能和经验应用于开发新的治疗方法， 被抗菌素耐药性混淆的眼部感染。这位候选人有一个突出的特点 在研究、培训和领导方面的成就记录。她成功地参加了独立竞选， 她拥有丰富的研究经费，富有创造力，工作努力，高度协作，并具有很强的沟通能力。 用导师自己的话说，货车泰恩博士“是K99/R 00奖的理想候选人”。 环境很适合候选人的提议。群众的眼睛和耳朵结合世界- 一流的临床实践和卓越的研究在一个单一的机构。眼科学系是一个 高质量的研究环境，许多研究人员能够与 候选人，并有提供成功的培训和职业发展的良好记录。的 传染病研究所保持了一个临床菌株收集，这将是一个独特的资源，利用这一点 项目吉尔摩实验室是慷慨资助，并可以提供额外的支持和资源， 候选人的项目。 候选人提出的研究计划包括三个目标。Aim 1将研究E.杆菌 在人的眼泪和血清中存活目标2将回答这个问题：粘液性如何改变宿主- 微生物动力学目标3将利用比较基因组学方法来比较大群体的革兰氏- 阴性眼部细菌病原体与来自其他感染部位的细菌，以确定遗传特征 有助于组织向性。