Staphylococcal Biofilms in Allergic Disease

过敏性疾病中的葡萄球菌生物膜

基本信息

批准号：
9308491
负责人：
ANDREW B HERR
金额：
$ 29.58万
依托单位：
CINCINNATI CHILDRENS HOSP MED CTR
依托单位国家：
美国
项目类别：
财政年份：
2006
资助国家：
美国
起止时间：
2006-09-15 至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9308491
关键词：
Adhesions Adhesives Administrative Supplement Affect Allergic Disease Allergic inflammation Allergic rhinitis Antibiotic Resistance Asthma Atopic Dermatitis Bacteria Behavior Biochemical Cell Wall Cells Characteristics Child Childhood Asthma Chronic Clinical Code Collection Crystallization DNA Data Dermatologic Dermatology Desmosomes Disease Dominant-Negative Mutation Duct (organ) structure Epidermis Epithelial Equilibrium Event Exhibits Filament Food Hypersensitivity Fostering Functional disorder Genes Genus staphylococcus Gills Growth Human Image Immune response Individual Inflammation Inflammatory Inflammatory Response Ions Journals Knock-out Lesion Link Measures Mediating Membrane Proteins Metals Methods Microbial Biofilms Molecular Nature Nose Pathogenesis Patients Peptide Hydrolases Polysaccharides Prevalence Process Protease Inhibitor Proteins Pruritus PubMed Recombinants Relapse Risk Role Sampling Severities Skin Staphylococcus aureus Staphylococcus epidermidis Statistical Data Interpretation Structure Surface Surveys Sweat Symbiosis TLR2 gene Taiwan Testing Thermodynamics Toxin Translational Research Variant Zinc allergic response antimicrobial antimicrobial peptide base cohort commensal microbes cytokine eccrine experimental study extracellular keratinocyte keratinocyte differentiation mechanical properties microbial microbial colonization microorganism interaction nanoscale next generation sequencing parent grant poly-N-acetyl glucosamine response skin barrier skin disorder skin lesion skin microbiome staphylococcal protease success synergism translational medicine ward

项目摘要

Modified Project Summary/Abstract Section Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that affects 15-20% of children worldwide. In addition to the characteristic lesions accompanied by intense itching, AD increases the risk of microbial colonization and allergic responses including food allergy, allergic rhinitis, and asthma, in a process referred to as the atopic march. It was noted over 40 years ago that AD lesions were frequently colonized by Staphylococcus aureus. Recently, lesions from AD patients were discovered to be colonized by both S. aureus and S. epidermidis strains that formed biofilms, which are adhesive surface-attached colonies that become highly resistant to antibiotics and immune responses. S. epidermidis is a normal skin commensal that in some contexts can antagonize S. aureus biofilm growth. However, we have found that S. aureus and S. epidermidis are capable of forming synergistic mixed biofilms when co-cultured, which is consistent with recent skin microbiome surveys showing increased prevalence of both S. aureus and S. epidermidis on AD lesional skin. Data from our lab and others has shown that staphylococcal biofilm growth is dependent on intercellular adhesion events mediated by the Aap and SasG proteins expressed on the surfaces of S. epidermidis and S. aureus, respectively. It has recently been shown that Aap and SasG can mediate heterophilic adhesion events between S. epidermidis and S. aureus cells. Our central hypothesis is that such heterophilic protein adhesion events facilitate the growth of strong mixed-species staphylococcal biofilms on AD lesional skin, which promote inflammation, compromise skin barrier function, and result in more severe AD and progression to asthma. Through the proposed aims, we will 1) test whether heterophilic protein interactions between Aap and SasG allow synergistic growth of mixed-species biofilms between Staphylococcus spp colonizing AD but not normal skin; 2) delineate the mechanistic basis by which mixed biofilms promote disease; and 3) test whether synergistic staphylococcal strains that make the strongest mixed biofilms are associated with AD severity, barrier dysfunction, and progression to asthma in M-PAACH children.

修改后的项目摘要/摘要部分特应性皮炎 (AD) 是一种慢性、复发性炎症性皮肤病，影响全球 15-20% 的儿童。除了伴有剧烈瘙痒的特征性病变外，AD 还增加了微生物定植和过敏反应的风险，包括食物过敏、过敏性鼻炎和哮喘，这一过程被称为特应性进行曲。 40 多年前人们就注意到 AD 病变经常被金黄色葡萄球菌定植。最近，发现 AD 患者的病变处被金黄色葡萄球菌和表皮葡萄球菌菌株定殖，形成生物膜，这些生物膜是粘附在表面的菌落，对抗生素和免疫反应具有高度抵抗力。表皮葡萄球菌是一种正常皮肤共生菌，在某些情况下可以拮抗金黄色葡萄球菌生物膜的生长。然而，我们发现金黄色葡萄球菌和表皮葡萄球菌共培养时能够形成协同混合生物膜，这与最近的皮肤微生物组调查一致，显示金黄色葡萄球菌和表皮葡萄球菌在 AD 病变皮肤上的患病率增加。我们实验室和其他实验室的数据表明，葡萄球菌生物膜的生长取决于分别在表皮葡萄球菌和金黄色葡萄球菌表面表达的 Aap 和 SasG 蛋白介导的细胞间粘附事件。最近表明，Aap 和 SasG 可以介导表皮葡萄球菌和金黄色葡萄球菌细胞之间的异嗜性粘附事件。我们的中心假设是，这种异嗜蛋白粘附事件促进了 AD 病变皮肤上强烈的混合物种葡萄球菌生物膜的生长，从而促进炎症，损害皮肤屏障功能，并导致更严重的 AD 和进展为哮喘。通过所提出的目标，我们将 1) 测试 Aap 和 SasG 之间的异嗜蛋白相互作用是否允许定植 AD 的葡萄球菌属物种之间的混合物种生物膜协同生长，但不能协同生长正常皮肤； 2）描述混合生物膜促进疾病的机制基础； 3) 测试产生最强混合生物膜的协同葡萄球菌菌株是否与 M-PAACH 儿童的 AD 严重程度、屏障功能障碍和哮喘进展相关。