Microbial Genomics Section, National Human Genome Research Institute, NIH, Bethesda, MD 20892, USA.
Metaorganism Immunity Section, Laboratory of Immune System Biology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, MD 20892, USA.
Cell Host Microbe. 2021 Feb 10;29(2):210-221.e6. doi: 10.1016/j.chom.2020.12.002. Epub 2020 Dec 31.
Candida auris is an emerging multi-drug-resistant human fungal pathogen. C. auris skin colonization results in environmental shedding, which underlies hospital transmissions, and predisposes patients to subsequent infections. We developed a murine skin topical exposure model for C. auris to dissect risk factors for colonization and to test interventions that might protect patients. We demonstrate that C. auris establishes long-term residence within the skin tissue compartment, which would elude clinical surveillance. The four clades of C. auris, with geographically distinct origins, differ in their abilities to colonize murine skin, mirroring epidemiologic findings. The IL-17 receptor signaling and specific arms of immunity protect mice from long-term C. auris skin colonization. We further determine that commonly used chlorhexidine antiseptic serves as a protective and decolonizing agent against C. auris. This translational model facilitates an integrated approach to develop strategies to combat the unfolding global outbreaks of C. auris and other skin-associated microbial pathogens.
耳念珠菌是一种新兴的抗多种药物的人类真菌病原体。耳念珠菌的皮肤定植会导致环境脱落，这是医院传播的基础，并使患者易随后感染。我们开发了一种用于耳念珠菌的小鼠皮肤局部暴露模型，以剖析定植的风险因素，并测试可能保护患者的干预措施。我们证明，耳念珠菌在皮肤组织隔室中建立了长期居留，这将逃避临床监测。具有不同地理起源的耳念珠菌的四个谱系在其在小鼠皮肤中定植的能力上存在差异，反映了流行病学发现。IL-17 受体信号和特定的免疫途径保护小鼠免受长期耳念珠菌皮肤定植。我们进一步确定，常用的洗必泰防腐剂可用作对抗耳念珠菌的保护和去定植剂。这种转化模型促进了一种综合方法的发展，以对抗耳念珠菌和其他与皮肤相关的微生物病原体的全球爆发。
