Mechanisms of staphylococcal skin colonization

葡萄球菌皮肤定植机制

• 批准号: 10449721
• 负责人: PAUL D FEY
• 金额: $ 65.07万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2022-03-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10449721
• 关键词: Address; Adherence; Adhesions; Binding; Biological Assay; Biology; Biophysics; Cell Wall; Coagulase; Crystallization; Data; Development; Disease; Family member; Genus staphylococcus; Glycoproteins; Goals; Human; Human Volunteers; Immune response; Immune system; Immunocompromised Host; Infection; Knowledge; Lectin; Ligand Binding; Ligands; Link; Mammals; Mediating; Membrane Proteins; Modality; Modeling; Mucous Membrane; Polysaccharides; Protein Region; Proteins; Rod; Role; Site-Directed Mutagenesis; Skin; Skin colonization; Specificity; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus hominis; Structure; Surface; Systems Development; Techniques; Testing; antimicrobial; base; commensal bacteria; design; experimental study; human pathogen; mouse model; novel therapeutics; pathogen; protein function; prototype; skin microbiota; sortase

ABSTRACT The goal of this Multi-PI project is to understand how Staphylococcus spp. bind to the skin surface. Although S. aureus has the capability to cause significant disease in humans, most Staphylococcus spp. do not cause disease but instead act as commensals or mutualists and adhere to the skin surface providing beneficial aspects to the host. These benefits include inhibition of pathogen colonization by synthesis of unique antimicrobial compounds in addition to appropriate immune system development. However, we do not know how Staphylococcus spp adhere to skin. This application hypothesizes that species of staphylococci that colonize humans do so in a conserved manner via an Aap (or SasG in S. aureus) orthologue that binds corneocytes. Aap is a rod-like fibrillar protein that functions in initial adherence to corneocytes but also functions to mediate intercellular accumulation. To address this hypothesis, we have proposed the following specific aims: (1) understand the dynamics of Aap-mediated corneocyte adherence; (2) define the ligand specificity of Aap and SasG lectin domains and (3) investigate S. aureus SasG-dependent mechanisms of skin colonization. Overall, the proposed studies will address how staphylococci bind to skin, what ligand is bound, and thus could uncover new layers of crosstalk between pathogen and the host, potentially leading to novel therapeutic modalities for treating staphylococcal infections.

摘要 本多PI项目的目标是了解葡萄球菌属如何在临床上应用。与皮肤表面结合。虽然S. 金黄色葡萄球菌具有在人类中引起重大疾病的能力，大多数葡萄球菌属（Staphylococcus spp.）不会引起 疾病，而是作为共生体或互惠体并粘附到皮肤表面，提供有益的方面 给主人。这些益处包括通过合成独特的抗微生物剂来抑制病原体定殖。 除了适当的免疫系统发展。然而，我们不知道如何 葡萄球菌属粘附于皮肤。这项应用假设，种葡萄球菌，殖民 人类以保守的方式通过Aap（或S.金黄色葡萄球菌）的直向同源物，其结合角质细胞。AAP 是一种杆状纤维蛋白，其在最初粘附于角质细胞中起作用，但也起到介导 细胞间积累为了解决这一假设，我们提出了以下具体目标：（1） 了解Aap介导的角质细胞粘附的动力学;（2）确定Aap的配体特异性， SasG凝集素结构域;金黄色葡萄球菌SasG依赖的皮肤定植机制。总的来说， 这项研究将解决葡萄球菌如何与皮肤结合，结合什么样的配体，从而揭示 病原体和宿主之间的新的串扰层，可能导致新的治疗方式， 治疗葡萄球菌感染。