Biofilm Formation by Listeria monocytogenes

单核细胞增生李斯特菌形成生物膜

• 批准号: 7408120
• 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 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7408120
• 关键词: Adhesions; Antibiotics; Bacteria; Biocide; Bioinformatics; Biology; Cell surface; Cell-Cell Adhesion; Cells; Childhood; Communicable Diseases; DNA Microarray Chip; DNA Microarray format; Decontamination; Detergents; Development; Disease Outbreaks; Economics; Environment; Fetus; Flagella; Food; Food Industry; Food Processing; Foundations; Gene Expression Profiling; Genes; Genetic; Genomics; Goals; Gram-Positive Bacteria; Human; Immune system; Immunocompromised Host; Individual; Infection; Ingestion; Lead; Life; Listeria; Listeria monocytogenes; Listeriosis; Mediating; Medicine; Mentors; Metabolism; Microarray Analysis; Microbial Biofilms; Microbiology; Microscopy; Molecular; Molecular Genetics; Mutagenesis; Newborn Infant; Numbers; Pathogenesis; Personal Satisfaction; Physiological; Positioning Attribute; Pregnant Women; Prevention; Program Development; Proteins; Research; Research Personnel; Resistance; Role; Source; Surface; Training; Variant; Work; career; cell motility; design; field study; food preparation; foodborne pathogen; insight; medical schools; microbial; mutant; novel strategies; prevent; professor; research study; surface coating; tool

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（由申请人提供）：项目摘要：此申请详细介绍了一项为期五年的研究职业发展计划，旨在探索在哈佛医学院的微生物学和分子遗传学系教授罗伯托·科尔特（Roberto Kolter）的指导下，探索食品传播病原体李斯特氏菌。 Kolter博士是微生物生物膜开发领域的领导者，并具有指导学员担任独立研究人员的出色记录。我的长期目标是成为一名独立的临床医生研究者。为此，我曾接受过小儿传染病和生物学的培训。该建议旨在使我成为一名独立研究人员，研究单核细胞增生李斯特菌的生物膜形成。这个研究领域与我先前的研究大不相同，我的计划包括细菌代谢和生物信息学的课程。革兰氏阳性细菌单核细胞增生菌是一种食物传播的病原体，会引起胎儿，新生儿和免疫功能低下的人的严重甚至致命的感染。 L.单核细胞增生物以生物膜形式持续存在于食物制备表面，这是导致李斯特菌病暴发的污染来源。生物膜是高度组织的，基质封闭的微生物细胞组合。与医学和食品工业特别相关的是，生物膜细菌比单个自由生活细菌更耐洗涤剂，杀菌剂和抗生素。这使得对生物膜涂层的表面进行净化特别困难。尽管对李斯特菌如何形成生物膜知之甚少，但对李斯特菌发病机理进行了充分的研究。结果，可以使用许多遗传和基因组工具。本文提出的实验旨在确定：（1）使用转座子和靶向诱变形成的生物膜形成需要哪些L.单核细胞增生基因，以及（2）使用DNA Microarray Technology的单细胞基因杆菌的单个自由生活细菌与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洞察力应导致新的方法来污染生物膜涂层的表面，并更好地了解生物膜。相关性：通过消除感染来源的预防仍然是继续努力减少传染病的人类和经济损失的基石。摄入被李斯特菌单核细胞增生疫苗污染的食物会引起新生儿，孕妇和患有免疫系统受损的人的严重，有时是致命的感染。我提出的研究将奠定基础，以理解单核细胞增生李斯特菌在表面上的生物膜中如何持续存在，例如食品加工中心的李斯特氏核细胞增生，在那里它可以成为感染的来源。