Proteomic Analyses of Clostridium difficile Spore Germination Apparatus

艰难梭菌孢子萌发装置的蛋白质组学分析

基本信息

批准号：
8020041
负责人：
Richard Helm
金额：
$ 22.33万
依托单位：
VIRGINIA POLYTECHNIC INST AND ST UNIV
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-03-01 至 2013-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8020041
关键词：
Affect Antibiotic Resistance Antibiotic Therapy Bacillus (bacterium)Bacillus anthracis Bacillus anthracis spore Bacillus cereus Bacillus subtilis Bacterial Spores Bioinformatics Cataloging Catalogs Cells Cessation of life Chemicals Clostridium Clostridium difficile Clostridium perfringens Code Colitis Communicable Diseases Communities Data Data Set Decontamination Development Diarrhea Disease Disinfection Effectiveness Environment Equipment Food Food Poisoning Frequencies Genes Germination Hospitals Individual Infection Infectious Agent Knowledge Laboratories Learning Left Mechanics Membrane Methods Modeling Morbidity - disease rate Pathway interactions Patients Peptidoglycan Phosphoproteins Phosphorylation Play Poisoning Population Preparation Procedures Process Property Protein Kinase Proteins Proteome Proteomics Protocols documentation Reagent Relapse Reproduction spores Research Research Personnel Resistance Role Signal Pathway Signal Transduction Site Time Variant antimicrobial botulinum cell type experience food preparation human disease killings method development mortality novel public health relevance receptor response ward

项目摘要

DESCRIPTION (provided by applicant): Bacterial endospores are agents of infectious disease, potential bioweapons, and causes of food spoilage and poisoning. The most notorious among these is Clostridium difficile-associated disease (CDAD) which continues to become more widespread as well are more severe. Elimination of spores from contaminated sites or materials is challenging due to the extreme resistance of these cell types to conventional antimicrobial treatments. Spores that have been triggered to germinate and lose dormancy are much more susceptible to antimicrobial treatments. Activation of a spore's native germination apparatus is a viable strategy for increasing the effectiveness of spore-killing methods. Dormant spores contain highly efficient machinery for sensing favorable changes in their environment and triggering germination. However, even under ideal laboratory germination conditions, up to 5% of a spore population will remain dormant. These "superdormant" spores are resistant to decontamination and are a potential cause of infection at later dates. The proposed research will catalog and quantify the proteomes of the membrane fractions of dormant, germinating, and superdormant spores of the species Bacillus anthracis, Bacillus subtilis, C. difficile, and Clostridium perfringens. Proteome similarities and differences between species will contribute to our understanding of the mechanics of spore germination signaling and progression. Proteome differences between rapidly-germinating and superdormant spores will indicate potential causes of superdormancy. This data will be used to develop models for how the signaling apparatus involved in initiation of germination contributes to superdormancy. Results of the studies will guide further studies on spore germination and the development of more efficient methods of spore decontamination. PUBLIC HEALTH RELEVANCE: Dormant bacterial spores are agents of infectious disease, potential bioweapons, and causes of food spoilage and poisoning. If spores can be caused to germinate, then they are much more susceptible to decontamination treatments. This research will reveal details of the natural germination apparatus, so that better methods for triggering germination can be devised.

描述（由申请人提供）：细菌内生孢子是传染病的媒介、潜在的生物武器以及食物腐败和中毒的原因。其中最臭名昭著的是艰难梭菌相关疾病（CDAD），它的传播范围越来越广，也越来越严重。由于这些细胞类型对传统抗菌处理具有极强的抵抗力，因此从受污染的场所或材料中消除孢子具有挑战性。被触发发芽并失去休眠的孢子更容易受到抗菌治疗的影响。激活孢子的天然萌发装置是提高孢子杀灭方法有效性的可行策略。休眠孢子含有高效的机制，可以感知环境中有利的变化并触发发芽。然而，即使在理想的实验室萌发条件下，多达 5% 的孢子种群仍处于休眠状态。这些“超级休眠”孢子对净化有抵抗力，是以后感染的潜在原因。拟议的研究将对炭疽芽孢杆菌、枯草芽孢杆菌、艰难梭菌和产气荚膜梭菌的休眠、发芽和超休眠孢子的膜部分的蛋白质组进行编目和量化。物种之间蛋白质组的相似性和差异将有助于我们理解孢子萌发信号和进展的机制。快速发芽和超级休眠孢子之间的蛋白质组差异将表明超级休眠的潜在原因。该数据将用于开发模型，了解参与发芽启动的信号装置如何促进超级休眠。研究结果将指导对孢子萌发的进一步研究和开发更有效的孢子净化方法。公共卫生相关性：休眠细菌孢子是传染病的病原体、潜在的生物武器以及食物腐败和中毒的原因。如果可以使孢子发芽，那么它们就更容易受到净化处理的影响。这项研究将揭示自然发芽装置的细节，以便设计出更好的触发发芽的方法。