Mechanisms of Candida auris Colonization in the Skin

耳念珠菌在皮肤中定植的机制

基本信息

批准号：
10717197
负责人：
Shankar Thangamani
金额：
$ 59.55万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-18 至 2027-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10717197
关键词：
Address Antibiotics Antifungal Agents Azoles Bacteria Bioinformatics Blood CRISPR/Cas technology Candida Candida auris Cells Centers for Disease Control and Prevention (U.S.)Classification Clinical Treatment Clinical Trials Coagulase Data Dendritic Cells Disease Outbreaks Environment Exhibits FDA approved Family suidae Fungal Genes Future Gene Expression Genes Genus staphylococcus Goals Growth Hospitalization Host Defense Human IL17 gene ITGAX gene Immune Immunologic Factors In Vitro Individual Infection Infectious Skin Diseases Integration Host Factors Intervention Knowledge Langerhans cell Life Mass Spectrum Analysis Mediating Metabolism Molecular Multiple Fungal Drug Resistance Mus Nursing Homes Pathogenesis Patients Play Polyenes Regulation Reporting Resistance Risk Factors Role Sequence Analysis Skin Skin Tissue Skin colonization Staphylococcus epidermidis Staphylococcus hominis Systemic infection TACSTD1 gene Testing Therapeutic Topical application Virulence Factors Wild Type Mouse antimicrobial antimicrobial peptide cathelicidin antimicrobial peptide commensal bacteria genome analysis gut colonization implantable device in vitro Assay in vivo microbiota mortality mouse model novel novel strategies novel therapeutic intervention pathogen pathogenic bacteria pathogenic fungus prevent recruit skin microbiota small molecule transcriptome sequencing transmission process

项目摘要

Project Summary Candida auris (CA), an emerging multi-drug resistant fungal pathogen that predominately colonizes in the skin has recently been classified as an urgent threat by the US Centers for Disease Control and Prevention (CDC) Antibiotic Threats Report. CA asymptomatically colonizes the skin for prolonged periods and rapidly spreads between hospitalized patients and nursing home residents via nosocomial transmission resulting in outbreaks of systemic infections. CA gains access to the blood in patients requiring indwelling devices leading to invasive infections resulting in mortality ranging from 40 to 60 percent among CA infected patients. Majority of CA isolates exhibit resistance to all three classes of FDA-approved antifungal drugs including azoles, polyenes, and echinocandins posing a significant challenge to treat this fungal pathogen. Therefore, understanding the factors regulating CA skin colonization is important to control CA outbreaks and prevent invasive CA infections. Recently, we have uncovered that skin microbiota regulate the CA skin colonization. Based on our compelling data, we will define the microbiota and host mediated mechanism(s) that control CA skin colonization. In Aim 1, we will define how skin microbiota directly inhibit CA growth and skin colonization and In Aim 2, we will define the host-mediated mechanisms through which skin microbiota regulate CA skin colonization. Understanding the microbiota and host factors in the regulation of CA is expected to lead to a more complete understanding of the factors that control CA skin colonization, with the long-term aim of identifying new antifungal therapeutic strategies.

项目概要耳念珠菌 (CA)，一种新兴的多重耐药真菌病原体，主要定植于皮肤中最近被美国疾病控制与预防中心 (CDC) 列为紧急威胁抗生素威胁报告。 CA 无症状地在皮肤上长时间定殖并迅速扩散住院患者和疗养院居民之间通过院内传播导致疫情暴发全身感染。 CA 可以获取需要留置装置的患者的血液，从而导致侵入性 CA 感染患者的死亡率为 40% 至 60%。大多数 CA 分离株对 FDA 批准的所有三类抗真菌药物（包括唑类、多烯类和棘白菌素对治疗这种真菌病原体构成了重大挑战。因此，了解这些因素调节 CA 皮肤定植对于控制 CA 爆发和预防侵袭性 CA 感染非常重要。最近，我们发现皮肤微生物群调节 CA 皮肤定植。基于我们令人信服的根据数据，我们将定义控制 CA 皮肤定植的微生物群和宿主介导机制。在目标 1 中，我们将定义皮肤微生物群如何直接抑制 CA 生长和皮肤定植，在目标 2 中，我们将定义皮肤微生物群通过宿主介导的机制调节 CA 皮肤定植。了解 CA 调节中的微生物群和宿主因素有望使人们更全面地了解 CA 控制 CA 皮肤定植的因素，长期目标是确定新的抗真菌治疗方法策略。