Mechanisms of staphylococcal skin colonization

葡萄球菌皮肤定植机制

• 批准号: 10595679
• 负责人: PAUL D FEY
• 金额: $ 53.43万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-22 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10595679
• 关键词: Address; Adherence; Adhesions; Atomic Force Microscopy; Binding; Biological Assay; Biology; Cell Wall; Coagulase; 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; Publishing; Rod; Role; Site-Directed Mutagenesis; Skin; Skin colonization; Specificity; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Staphylococcus hominis; Structure; Surface; Systems Development; Techniques; Testing; antimicrobial; biophysical properties; 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.

抽象的 这个多PI项目的目标是了解葡萄球菌属。结合皮肤表面。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。不要引起 疾病，而是充当共生主义者或共同主义者，并遵守皮肤表面提供有益的方面 到主持人。这些好处包括通过合成独特的抗菌剂来抑制病原体定植 除了适当的免疫系统开发外，化合物。但是，我们不知道如何 葡萄球菌spp粘附在皮肤上。该应用假设葡萄球菌的种类定居 人类通过结合角膜细胞的AAP（或金黄色葡萄球菌中的SASG）以保守的方式进行。 AAP 是一种棒状的纤维蛋白 细胞间积累。为了解决这一假设，我们提出了以下特定目的：（1） 了解AAP介导的角膜粘附的动力学； （2）定义AAP的配体特异性和 SASG凝集素结构域和（3）研究了皮肤定植的金黄色葡萄球菌SASG依赖性机制。全面的， 拟议的研究将解决葡萄球菌如何与皮肤结合，配体的结合，因此可以发现 病原体与宿主之间的串扰新层，有可能导致新的治疗方式 治疗葡萄球菌感染。