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.

接触透镜相关的眼部感染每年影响数百万人。透镜护理的标准指南可以使眼睛感染最小化，但是已经显示只有大约50%的透镜佩戴者遵守适当的指南。在通常的使用和储存过程中，微生物粘附在隐形眼镜上。日常透镜清洁去除了这些微生物中的大部分，但是有时微生物在透镜上建立生物膜，并且尽管使用目前可用的系统进行消毒和清洁，但是通常这种生物膜不能令人满意地去除。在许多情况下，微生物的来源是透镜的情况，其中已经形成生物膜。 除了对透镜消毒剂/清洁系统的抗性之外，由病原生物体形成的生物膜由于其对抗生素和宿主免疫应答的抗性以及其在留置医疗装置上生长的能力而具有越来越大的临床重要性。一氧化氮（NO）已被证明通过产生NO的粒细胞的作用有效地杀死哺乳动物宿主中的细菌和真菌。我们先前已经利用NO的抗微生物特性来产生能够杀死真菌和非稳态生长的细菌的缓慢NO释放化合物。在本研究中，我们将测试这样的化合物也能够杀死在已建立的生物膜中生长的生物体的原理。在这种情况下，第一阶段提案的目的是检验NO治疗能够杀死 包含由接触透镜相关眼睛感染的病原体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NO处理的敏感性。 如果获得原理证明，则II期研究的最终目标是开发用于透镜和透镜盒灭菌的适当输送载体。我们将在第一阶段启动这项工作，并在此讨论可能的方法。