Exfoliative toxin A and desmosomal adhesion in epidermis

剥脱性毒素A与表皮桥粒粘附

• 批准号: 7158275
• 负责人: Cory L Simpson
• 金额: $ 3.35万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7158275
• 关键词: Staphylococcus aureus; bacteria infection mechanism; bacterial toxicology; bacterial toxins; cadherins; cell adhesion; cell migration; intercellular connection; intermolecular interaction; keratinocyte; pathologic process; predoctoral investigator; skin disorder; tissue /cell culture

DESCRIPTION (provided by applicant): Exfoliative toxin A (ETA) secreted by Staphylococcus aureus causes destruction of human epidermis in bullous impetigo and Staphylcoccal Scalded Skin Syndrome (SSSS), which renders victims vulnerable to life-threatening infections and dehydration. Desmosomes are crucial for cell:cell adhesion in tissues enduring stress, such as the epidermis. These protein complexes anchor intermediate filaments to celhcell junctions, providing the mechanical strength necessary for the skin to serve as the body's first line of defense against environmental insults. Previous work has shown that ETA cleaves desmoglein 1 (Dsg1), a desmosome component and the predominant cadherin of the superficial epidermis. The proposed research will determine the specific molecular consequences of Dsg1 cleavage by ETA that contribute to SSSS. In particular, the toxin's effects on trafficking of and interactions among desmosomal components will be investigated as mechanisms reducing adhesion in keratinocytes; as well, a decoy Dsg1 ectodomain will be evaluated as an ETA inhibitor in vitro and in epidermal equivalents. The results will provide a more complete understanding of SSSS pathogenesis and will identify novel therapeutic targets for treatment of a toxin-mediated disease.

描述（由申请人提供）：金黄色葡萄球菌分泌的去角质毒​​素A（ETA）在大胆的疫苗和葡萄球菌烧伤的皮肤综合征（SSS）中造成人类表皮的破坏，这使受害者受害者受害者生命中的感染和脱发。脱骨小体对细胞至关重要：细胞粘附在持续应激的组织中，例如表皮。这些蛋白质复合物将中间细丝锚定在Celhcell连接处，为皮肤提供了作为人体对环境侮辱的第一道防线所必需的机械强度。先前的工作表明，ETA裂解去木蛋白1（DSG1），一种浅表成分和浅表表皮的主要钙粘着蛋白。拟议的研究将确定dsg1裂解对SSSS的特定分子后果。特别是，将研究毒素对脱染色体成分的运输和相互作用的影响，以减少角质形成细胞的粘附机制；同样，将在体外和表皮等效物中评估诱饵DSG1外生域。结果将为SSSS发病机理提供更完整的了解，并确定用于治疗毒素介导的疾病的新型治疗靶标。