Biofilm development and Eye Infections

生物膜形成和眼部感染

• 批准号: 6885640
• 负责人: Robert Raulli
• 金额: $ 11.72万
• 依托单位: AMULET PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6885640
• 关键词: antibacterial agents; antifungal agents; antisepsis; biofilm; contact lens; disinfectants; drug design /synthesis /production; drug screening /evaluation; environmental contamination; eye infections; nitric oxide

Contact lens related eye infections impact millions of people yearly. Standard guidelines for lens care can minimize eye infection, but it has been shown that only about 50% of lens wearers adhere to appropriate guidelines. During usual use and storage procedures, microorganisms adhere to contact lenses. Daily lens cleaning removes most of these microorganisms, but sometimes microbes establish biofilms on lenses and often such biofilms are not satisfactorily removed despite disinfection and cleaning with systems currently available. In many cases the source of the microorganisms is the lens case where biofilms have developed. In addition to resistance to lens disinfectant/cleaning systems, biofilms formed by pathogenic organisms are of increasing clinical importance due to their resistance to antibiotics and host immune responses as well as their ability to develop on indwelling medical devices. Nitric oxide (NO) has been shown to efficiently kill bacteria and fungi in the mammalian host by the action of granulocytes that produce NO. We have previously exploited the antimicrobial properties of NO to create slow NO releasing compounds that are capable of killing both fungi and bacteria growing planktonically. In the present investigation, we will test the principle that such compounds are also capable of killing organisms growing in established biofilms. In this context, the aim of this Phase I proposal is to test the hypothesis that NO treatment is capable of killing microbial cells that comprise biofilms formed by causative agents of contact lens related eye infection. The sensitivity of appropriate bacterial, fungal, and mixed species biofilms to NO treatment will be determined. If proof of principle is obtained, the ultimate goal of the investigation to be pursued in Phase II is the development of an appropriate delivery vehicle for lens and lens case sterilization. We will initiate this work during Phase I, and possible approaches are also discussed herein.

与隐形眼镜相关的眼部感染每年影响数百万人。镜头护理的标准指南可以最大程度地减少眼部感染，但已显示仅约50％的镜头佩戴者遵守适当的指南。在通常的使用和储存过程中，微生物遵守隐形眼镜。每日镜头清洁消除了大多数这些微生物，但有时微生物在镜片上建立生物膜，尽管尽管使用了当前可用的系统，但经常不会令人满意地去除这种生物膜。在许多情况下，微生物的来源是生物膜开发的镜头情况。 除了对晶状体消毒/清洁系统的抗性外，致病生物形成的生物膜由于对抗生素的耐药性和宿主免疫反应以及在留置医疗设备上的发展能力而越来越重要。一氧化氮（NO）已证明可以通过产生NO的粒细胞的作用在哺乳动物宿主中有效杀死细菌和真菌。我们以前已经利用了NO的抗菌特性，以产生缓慢的NO释放化合物，这些化合物能够杀死真菌和细菌生长浮游。在本研究中，我们将测试这样的化合物也能够杀死在既定生物膜中生长的生物的原则。在这种情况下，I阶段I提议的目的是检验以下假设：没有治疗能够杀死 由隐形眼镜相关的眼感染的因子剂形成的生物膜的微生物细胞。将确定适当的细菌，真菌和混合物种生物膜对未治疗的敏感性。 如果获得原理证明，则在第二阶段进行调查的最终目标是开发适合晶状体和晶状体病例灭菌的递送工具。我们将在第一阶段开始这项工作，并在本文中讨论了可能的方法。