Extracellular ATP in biofilm formation and wound infection

细胞外 ATP 在生物膜形成和伤口感染中的作用

• 批准号: 8532935
• 负责人: Chuanwu Xi
• 金额: $ 27.66万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-10 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8532935
• 关键词: ATP Receptors; Acinetobacter baumannii; Adherence; Animal Model; Animals; Antibiotics; Apyrase; Bacteria; Bioinformatics; Biological; Burn injury; Cells; Communicable Diseases; Communities; Development; Effectiveness; Environment; Enzymes; Epithelial Cells; Escherichia coli; Extracellular Space; Growth; Heat shock proteins; Hemorrhage; Host Defense; Immune; Immune response; Immune system; In Vitro; Infection; Inflammatory; Inflammatory Response; Injury; Invaded; Lead; Leukocytes; Literature; Local Anti-Infective Agents; Mechanics; Mediating; Medicine; Microarray Analysis; Microbial Biofilms; Molecular; Monitor; Morbidity - disease rate; Multi-Drug Resistance; Natural Immunity; Nature; Nosocomial Infections; Organism; Pathogenesis; Pathway interactions; Plants; Public Health; Recruitment Activity; Research; Resistance; Risk; Role; Signal Pathway; Signal Transduction; Site; Skin; Surface; Testing; Tissues; Wound Infection; cDNA Arrays; cell injury; cytokine; extracellular; heat injury; in vivo Model; injured; killings; microorganism; mortality; mouse model; novel strategies; novel therapeutics; pathogen; prevent; resistant strain; response; success; tool; wound

DESCRIPTION (provided by applicant): The inflammatory response and the innate immune system serve to 1) recruit immune cells to the wound, 2) contain and kill invading organisms and 3) clear the wound of noxious substances. However, wound infections are commonplace after thermal injuries and represent a major cause of morbidity and mortality. Bacteria that colonize the wound grow as adherent, multicellular communities known as biofilms and the biofilm mode of growth renders the bacterial cells resistant to killing by antiseptics, antibiotics and host defenses, which may explain the nature of many wound infections. Recently we found that exogenously added ATP can stimulate bacteria adherence and biofilm formation on abiotic and biotic surfaces and in a burn wound and previous studies in the literature found that injured epithelial cells release large amount ATP into the extracellular space, which serves as a "danger signal" and activate host innate immunity. Therefore, the major objective of this project is to define the role of extracellular ATP in bacteria-host interactions within the thermal injury. We hypothesize that extracellular ATP severs as an "inter-domain" signal and modulate both bacteria and host responses in the burn wound and can be a target for managing wound infections. To test this hypothesis, we will use both in vitro and in vivo models to elucidate molecular mechanisms of extracellular ATP signaling in bacteria using Acinetobater baumannii and E. coli as model organisms focusing on biofilm development and examine the inflammatory cytokines and leukocyte bacterial killing within thermal injuries by modulating extracellular ATP using the enzyme apyrase. Success of this study will enhance a more comprehensive and basic understanding of bacteria-host interactions and bacterial pathogenesis and will likely lead to the development of novel approaches to prevent/reduce wound infections and other infectious diseases.

描述（由申请人提供）：炎症反应和先天免疫系统可用于1）招募免疫细胞到伤口，2）包含并杀死入侵的生物； 3）清除有害物质的伤口。但是，伤口感染在热损伤后很常见，代表了发病率和死亡率的主要原因。在伤口上定居的细菌会随着粘附，多细胞群落的粘附而生长，被称为生物膜和生长模式，使细菌细胞具有抗药性，抗生素和宿主防御能力的抗性细菌细胞，这可能解释了许多伤口感染的性质。最近，我们发现，外源添加的ATP可以刺激非生物和生物表面上的细菌粘附和生物膜形成，并且在烧伤的伤口和文献中的先前研究中发现，受伤的上皮细胞将大量ATP释放到细胞外空间中，这是“危险信号”，并激活宿主的天生免疫。因此，该项目的主要目的是定义细胞外ATP在热损伤中细菌宿主相互作用中的作用。我们假设细胞外的ATP将其作为“域间”信号，并调节烧伤伤口中的细菌和宿主反应，并且可以成为控制伤口感染的靶标。为了检验这一假设，我们将使用体外和体内模型阐明细胞外ATP信号传导的分子机制，使用鲍曼省Aacinetobater和大肠杆菌在细菌中和大肠杆菌中作为模型生物体作为模型的生物体，作为对生物膜发育的重点，并检查炎症细胞和白细胞细胞造成的生物膜，并研究了伴随炎症性细胞的杀伤症。根酶。这项研究的成功将增强对细菌宿主相互作用和细菌发病机理的更全面和基本的理解，并可能导致开发新的方法，以预防/减少伤口感染和其他传染病。