The essential P. aeruginosa pan-genome during chronic infection

慢性感染过程中必需的铜绿假单胞菌全基因组

• 批准号: 8623447
• 负责人: Daniel J Wozniak
• 金额: $ 24.43万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8623447
• 关键词: Acinetobacter baumannii; Acute; Address; Antibiotics; Bacteria; Bacterial Infections; Behavior; Biology; Burn injury; Chronic; Clinical; Development; Disease; Dose; Endocarditis; Environment; Family suidae; Future; Genes; Genetic Determinism; Genome; Genomics; Growth; Health; Healthcare; Human; Immune system; Immunity; Infection; Knowledge; Learning; Life; Link; Methodology; Microbe; Microbial Biofilms; Mission; Modeling; Molecular; Nature; Operative Surgical Procedures; Organism; Pathogenesis; Pathway interactions; Pseudomonas aeruginosa; Public Health; Sampling; Site; Staphylococcus aureus; Swimming; Testing; Thick; Time; United States National Institutes of Health; Work; Wound Healing; Wound Infection; burden of illness; design; disability; enhancing factor; in vivo; information gathering; insight; novel; novel strategies; pathogen; public health relevance; research study; treatment strategy; wound

DESCRIPTION (provided by applicant): This application seeks to address the impact of bacterial colonization and persistence in chronic wounds. The formation of biofilms has clearly been linked to chronic and persistent bacterial infections. This considerably delays and complicates wound healing. Unlike acute bacterial infections, which are often cleared by the host, biofilm-related chronic infections are not easily resolved even with high dose antibiotics and intact immunity. The bacterial pathogens Pseudomonas aeruginosa, Acinetobacter baumannii, and Staphylococcus aureus, which are the focus of this application, cause an array of biofilm-related clinical diseases including persistent airway infections, burn wound infections, endocarditis, and surgical site infections. Unresolved infected wounds also contribute to nosocomial persistence and the spread of bacteria in health care settings. This proposal will use state-of-the art molecular and genomic approaches to define genes and pathways essential for P. aeruginosa persistence in chronic wounds in monoculture as well as in the presence of S. aureus and/or A. baumannii. Investigating this hypothesis will allow us to learn new P. aeruginosa biology and aid future management and treatment of chronic infections. Aim 1 will identify genes and pathways necessary for P. aeruginosa during a chronic wound infection. Aim 2 will identify genes and pathways necessary for P. aeruginosa during polymicrobial chronic wound infections. The development of a chronic infection model that can be sampled over time provides a relevant, unique, and novel approach for examining the effects of biofilm formation in the host. Ultimately information gathered will aid the treatment of an array of chronic infections including highly prevalent persistent wound infections.

描述（由申请人提供）：本申请旨在解决慢性伤口中细菌定植和持久性的影响。生物膜的形成显然与慢性和持续的细菌感染有关。这大大延迟了伤口愈合。与通常由宿主清除的急性细菌感染不同，即使使用高剂量抗生素和完整的免疫力，与生物膜相关的慢性感染也不容易解决。细菌病原体是铜绿假单胞菌，鲍曼尼杆菌和金黄色葡萄球菌（这是该应用的重点）引起一系列与生物膜相关的临床疾病的重点 心内膜炎和手术部位感染。未解决的感染伤口也有助于医疗保健环境中细菌的医生持久性和细菌的传播。该建议将使用最先进的分子和基因组方法来定义单一培养物以及金黄色葡萄球菌和/或Baumannii的慢性伤口中铜绿假单胞菌持久性必不可少的基因和途径。研究这一假设将使我们能够学习新的铜绿假单胞菌生物学，并帮助对慢性感染的未来管理和治疗。 AIM 1将在慢性伤口感染期间鉴定铜绿假单胞菌所需的基因和途径。 AIM 2将确定多因素慢性伤口感染期间铜绿假单胞菌所必需的基因和途径。可以随着时间的推移进行采样的慢性感染模型的开发提供了一种相关，独特和新颖的方法，用于检查宿主中生物膜形成的影响。最终收集的信息将有助于治疗一系列慢性感染，包括高度普遍的持续伤口感染。