Biofilm Formation by Listeria monocytogenes

单核细胞增生李斯特菌形成生物膜

• 批准号: 7130587
• 负责人: Katherine Paige Lemon
• 金额: $ 12.37万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7130587
• 关键词: Listeria; bacteria; biofilm

DESCRIPTION (provided by applicant): Project Summary: This application details a five year research career development program designed to explore biofilm formation by the food-borne pathogen Listeria monocytogenes under the guidance of Dr. Roberto Kolter, Professor in the Department of Microbiology and Molecular Genetics at Harvard Medical School. Dr. Kolter is a leader in the field of microbial biofilm development and has an excellent track record of mentoring his trainees to positions as independent investigators. My long-term goal is to become an independent clinician-researcher. To this end, I have trained in both pediatric infectious diseases and biology. This proposal is designed to prepare me to be an independent researcher studying biofilm formation by L. monocytogenes. This field of study is very different from my prior research and my plan includes coursework in bacterial metabolism and bioinformatics. The gram-positive bacterium L. monocytogenes is a food-borne pathogen that causes severe, even fatal, infections in fetuses, newborns, and immunocompromised people. L. monocytogenes persisting on food preparation surfaces in the form of biofilms is a source of contamination that leads to listeriosis outbreaks. Biofilms are highly organized, matrixenclosed assemblages of microbial cells. Of particular relevance to both medicine and the food industry, biofilm bacteria are more resistant to detergents, biocides, and antibiotics than are individual, free-living bacteria. This makes decontamination of biofilm-coated surfaces particularly difficult. Although little is known about how Listeria forms biofilms, Listeria pathogenesis is well studied. As a result, a number of genetic and genomic tools are available. The experiments proposed herein are designed to determine: (1) what L. monocytogenes genes are required for biofilm formation using transposon and targeted mutagenesis, and (2) what are the physiological differences between individual free-living bacteria and biofilm-associated bacteria for L. monocytogenes using DNA microarray technology. Insights gained from these experiments should lead to new approaches to decontaminate biofilm-coated surfaces, and a better understanding of biofilms in general. Relevance: Prevention by eliminating sources of infection remains a cornerstone in the continued effort to decrease the human and economic toll of infectious diseases. Ingestion of food contaminated with Listeria monocytogenes can cause severe, sometimes fatal, infections in newborns, pregnant women and people with compromised immune systems. The research I have proposed will lay the foundation for understanding how Listeria monocytogenes persists in the environment in biofilms on surfaces, such as those in food processing centers, where it can be a source of infection.

描述(申请人提供)：项目概要：本申请详细介绍了一个为期五年的研究职业发展计划，该计划旨在哈佛医学院微生物学和分子遗传学系教授Roberto Kolter博士的指导下，探索食源性单核细胞增多性李斯特菌生物膜的形成。科尔特博士是微生物生物膜开发领域的领导者，在指导受训人员担任独立调查人员方面有着出色的记录。我的长期目标是成为一名独立的临床医生和研究员。为此，我接受了儿科传染病和生物学方面的培训。这项提议是为了让我做好准备，成为一名研究单核细胞增多性乳杆菌生物膜形成的独立研究员。这一研究领域与我之前的研究非常不同，我的计划包括细菌新陈代谢和生物信息学的课程。革兰氏阳性菌单核细胞增多性乳杆菌是一种食源性病原体，会在胎儿、新生儿和免疫功能低下的人中引起严重，甚至致命的感染。单核细胞增多性乳杆菌以生物膜的形式存在于食品加工表面，是导致李斯特菌病暴发的污染源。生物膜是高度组织的、基质包裹的微生物细胞组合。与医药和食品工业特别相关的是，生物膜细菌比单个自由生活的细菌对洗涤剂、杀生剂和抗生素更具抵抗力。这使得生物膜涂层表面的去污变得特别困难。虽然对李斯特菌如何形成生物膜知之甚少，但对其发病机制已有较好的研究。因此，许多遗传和基因组工具都是可用的。本实验旨在确定：(1)利用转座子和靶向诱变技术形成生物膜需要哪些单核细胞增多性李斯特菌；(2)利用DNA微阵列技术，单核细胞增多性李斯特菌的个体自由生活细菌和生物膜相关细菌之间的生理差异是什么。从这些实验中获得的见解应该会导致新的方法来净化生物膜覆盖的表面，并从总体上更好地理解生物膜。相关性：通过消除感染源进行预防仍然是继续努力减少传染病造成的人和经济损失的基石。摄入受单核细胞增多性李斯特菌污染的食物会导致新生儿、孕妇和免疫系统受损的人受到严重的、有时是致命的感染。我提出的研究将为了解单核细胞增多性李斯特菌如何在环境中通过表面的生物膜存活奠定基础，例如食品加工中心的生物膜，在那里它可能是感染源。