Mechanisms of Candida auris Colonization in the Skin

耳念珠菌在皮肤中定植的机制

• 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
• 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

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 可以接触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 微生物群和宿主因素在 CA 调节中的作用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。