Biofilms and Immunity in Chronic Wounds

慢性伤口中的生物膜和免疫

• 批准号: 8414015
• 负责人: Chandan K Sen
• 金额: $ 42.21万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8414015
• 关键词: Acute; Address; Antibiotics; Architecture; Bacteria; Bacterial Infections; Burn injury; Cells; Characteristics; Chronic; Clinical; Communities; Data; Debridement; Development; Disease; Dose; Endocarditis; Family; Family suidae; Future; Genomics; Health; Healthcare; Host Defense; Human; Immune; Immune response; Immune system; Immunity; Impaired wound healing; In Vitro; Individual; Infection; Inflammatory; Kinetics; Link; Methods; Microbe; Microbial Biofilms; Mission; Modeling; Molecular; Molecular Profiling; Natural Immunity; Operative Surgical Procedures; Organism; Patients; Population; Pseudomonas aeruginosa; Public Health; Resistance; Sampling; Site; Staphylococcus aureus; Swimming; Testing; Thick; Time; Tissues; Trauma; Work; Wound Healing; Wound Infection; Wounds and Injuries; antimicrobial; base; cytokine; density; design; efficacy testing; human tissue; immune clearance; improved; in vitro Model; information gathering; insight; killings; microbial; non-genomic; novel strategies; pathogen; research study; response; 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 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. The abundance and persistence of chronic infections due to biofilm formation has led to the hypothesis that biofilms deploy directed mechanisms to subvert recognition, activation, and functions of the host immune system. This proposal will use state-of-the- art molecular and genomic approaches to better understand the impact of bacterial colonization in chronic wounds. Aim 1 will define mechanisms by which P. aeruginosa and S. aureus resist killing by host-derived antimicrobials and innate immune cells. Aim 2 will utilize a newly developed porcine full thickness burn chronic wound model and explanted human tissue from burn wound debridement to investigate biofilm persistent infections caused by P. aeruginosa and S. aureus. The development of a chronic infection model that can be sampled over time as well as access to materials derived from humans suffering burn-wound injury provides a relevant, unique, and novel approach for examining the effects of biofilm formation in the host. Conclusions made from in vitro data will be efficiently tested in the porcine model and human tissue for applicability in clinical infection. Ultimately information gathered will aid the treatment of an array of chronic infections including highly prevalent persistent wound infections. PUBLIC HEALTH RELEVANCE: Pseudomonas aeruginosa and Staphylococcus aureus are versatile opportunistic pathogens that can cause devastating persistent wound infections. Within the wound, these organisms transform into a resistant community called a biofilm. Biofilm-related chronic infections are not easily resolved even with high dose antibiotics and intact immunity. This application will use molecular and genomic approaches to define how biofilm-growing bacteria resist antibiotics and host immune cells. This will allow us to better understand the impact of bacterial colonization in chronic wounds and aid future management and treatment of chronic infections that significantly impact human health.

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和金黄色葡萄球菌，这是该应用的重点，引起了一系列与生物膜相关的临床疾病，包括持续性气道感染，烧伤伤口感染，内膜炎和外科手术部位感染。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。由于生物膜形成引起的慢性感染的丰度和持久性导致了一个假设，即生物膜部署了定向机制来颠覆宿主免疫系统的识别，激活和功能。该建议将使用最先进的分子和基因组方法更好地了解细菌定植在慢性伤口中的影响。 AIM 1将定义铜绿假单胞菌和金黄色葡萄球菌通过宿主衍生的抗微生物和先天免疫细胞杀死的机制。 AIM 2将利用新开发的猪全厚度烧伤慢性伤口模型，并通过烧伤伤口清创侵蚀人类组织，以研究由铜绿假单胞菌和金黄色葡萄球菌引起的生物膜持续感染。可以随着时间的推移进行采样的慢性感染模型的发展，以及从遭受烧伤损伤的人类衍生的材料的访问提供了一种相关，独特和新颖的方法，用于检查宿主中生物膜形成的影响。从体外数据制定的结论将在猪模型和人体组织中有效测试，以在临床感染中适用。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。 公共卫生相关性：铜绿假单胞菌和金黄色葡萄球菌是多功能的机会病原体，可能导致毁灭性的持续伤口感染。在伤口内，这些生物变成了一个称为生物膜的抗性社区。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。该应用将使用分子和基因组方法来定义生物生长的细菌如何抵抗抗生素和宿主免疫细胞。这将使我们能够更好地了解细菌定植对慢性伤口的影响，并有助于对慢性感染的未来管理和治疗，从而对人类健康产生重大影响。