Post-transcriptional regulation of biofilm formation S. aureus

生物膜形成的转录后调控金黄色葡萄球菌

基本信息

批准号：
7391713
负责人：
KIMBERLY Kay JEFFERSON
金额：
$ 28.71万
依托单位：
VIRGINIA COMMONWEALTH UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-04-01 至 2012-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7391713
关键词：
Address Affinity Chromatography Antibiotic Resistance Antibiotics Antimicrobial Resistance Bacteria Bacterial Adhesins Binding Binding Sites Biological Assay Carbohydrates Carbon Catheters Cell membrane Cells Clinical Communities Complex Condition Confocal Microscopy Crystallography Deletion Mutation Development Electrophoretic Mobility Shift Assay Emerging Communicable Diseases Endocarditis Exhibits Gel Gene Cluster Genes Genetic Transcription Glucosamine Glucose Goals Growth Half-Life Healthy People 2010 Immune system Immunodominant Antigens In Vitro Infection Investigation Laboratories Lead Length Link Medical Device Membrane Microbial Biofilms Modality Molecular Monitor Names Nosocomial Infections Nucleotides Numbers Organism Osteomyelitis Pathway interactions Personal Satisfaction Phagocytosis Plasmids Play Polymers Polysaccharides Population Post-Transcriptional Regulation Production Protein Binding Proteins RNA RNA Binding RNA-Binding Proteins Recombinants Refractory Regulation Relapse Repression Research Research Personnel Resistance Role Sepsis Series Source Staphylococcus aureus Structure Surface Techniques Therapeutic Therapeutic Agents Transcript Translating Translational Repression Translations UDP-glucosamine Untranslated Regions Uridine Diphosphate Glucose Virulence X ray microscopy X-Ray Crystallography antimicrobial base chemotherapy fighting genetic manipulation human tissue improved mutant novel pathogen prevent programs promoter

项目摘要

DESCRIPTION (provided by applicant): Staphylococcus aureus is one of the most common causes of nosocomial bloodstream infections and is also an important cause of endocarditis, osteomyelitis, and other infections. Antibiotic resistance in S. aureus is a serious clinical problem that is compounded by the ability of the organism to form a biofilm on human tissues and inserted medical devices such as catheters. Most strains of S. aureus are able, under the appropriate environmental conditions, to elaborate a surface-associated (3-1-6-linked polymer of N-acetyl-glucosamine (PNAG) that serves two significant virulence functions: 1. it functions as the major constituent of the biofilm exo-polymeric matrix and 2. it protects the bacteria from phagocytosis during infection. The development of a biofilm during infection often results in a bacterial population that is refractory to antimicrobial chemotherapy and can act as a smoldering nidus for relapsing infection. In addition, resistance to phagocytosis enables the bacteria to evade the immune system. Therefore, it is not surprising that the intercellular adhesin (ica) locus, which encodes four proteins, Ica A, IcaD, IcaB, and IcaC, that are involved in PNAG synthesis, appears to play a critical role in virulence. Current therapeutic modalities for S. aureus infections could be significantly improved by inhibiting the formation of a resistant biofilm. The long-term objective of this project is to characterize the regulation of PNAG elaboration and subsequent biofilm formation bv S. aureus. A thorough understanding of this pathway could lead to the identification of targets for anti-biofilm therapeutic agents to act svnergisticallv with conventional antibiotics. This addresses the Healthy People 2010 goal of fighting "Infectious Diseases and Emerging Antimicrobial Resistance" and goal 14-20 "Hospital Acquired Infections". We have isolated an RNA-binding protein that binds to ica transcript and appears to increase half-life of the RNA and inhibit translation. The immediate goal of this proposed project is to further characterize the post- transcriptional regulatory mechanism bv which this RNA-binding protein regulates ica expression and PNAG production. Short Description. Staphylococcus aureus is an important pathogen that can cause a variety of infections. Antibiotic resistance in S. aureus is common and the problem is compounded by its ability to form adherent, polysaccharide-encased communities called biofilms. The goal of our research is to characterize the mechanism by which biofilm formation is regulated in S. aureus. Understanding the mechanism of biofilm regulation could lead to the development of anti-biofilm therapies that would act synergistically with conventional antibiotics.

描述（由申请人提供）：金黄色葡萄球菌是医生血液感染的最常见原因之一，也是心内膜炎，骨髓炎和其他感染的重要原因。金黄色葡萄球菌中的抗生素耐药性是一个严重的临床问题，它因生物体在人体组织和插入的医疗设备（例如导管）上形成生物膜的能力而使抗生素抗性。金黄色葡萄球菌的大多数菌株在适当的环境条件下能够详细说明与表面相关的（3-1-6-连接的N-乙酰基葡萄糖胺（PNAG）的聚合物（PNAG），具有两个重要的毒力功能：1。它起作用，是生物生物基质的主要组成型，它是生物生物基质的开发过程。感染期间的生物膜通常会导致对抗菌化疗的细菌种群，并且可以作为复发性感染的闷热的Nidus。与PNAG合成有关的ICAC似乎在毒力中起着关键作用。该项目的长期目标是表征PNAG阐述的调节和随后的生物膜形成BV S.金黄色葡萄球菌。对这一途径的透彻理解可能导致鉴定抗生物膜治疗剂的靶标，以用常规的抗生素作用于SvnergisticAllv。这探讨了与“感染性疾病和新兴的抗菌素耐药性”和目标14-20“医院获得感染的目标”的健康目标。我们分离了一种与ICA转录物结合的RNA结合蛋白，似乎增加了RNA的半衰期并抑制翻译。该提出的项目的直接目标是进一步表征转录后调节机制BV，该RNA结合蛋白调节ICA表达和PNAG产生。简短描述。金黄色葡萄球菌是一种重要的病原体，可引起多种感染。金黄色葡萄球菌中的抗生素耐药性是常见的，并且该问题具有形成称为生物膜的粘附的，多糖的社区的能力。我们研究的目的是表征在金黄色葡萄球菌中调节生物膜形成的机制。了解生物膜调节的机制可能会导致抗生物膜疗法的发展，这些抗生物膜疗法将与常规抗生素协同作用。