Nemecek Julie C, Wüthrich Marcel, Klein Bruce S
Department of Medical Microbiology and Immunology, University of Wisconsin Medical School, University of Wisconsin Hospital and Clinics, Madison, WI 53792, USA.
Science. 2006 Apr 28;312(5773):583-8. doi: 10.1126/science.1124105.
Microbial pathogens that normally inhabit our environment can adapt to thrive inside mammalian hosts. There are six dimorphic fungi that cause disease worldwide, which switch from nonpathogenic molds in soil to pathogenic yeast after spores are inhaled and exposed to elevated temperature. Mechanisms that regulate this switch remain obscure. We show that a hybrid histidine kinase senses host signals and triggers the transition from mold to yeast. The kinase also regulates cell-wall integrity, sporulation, and expression of virulence genes in vivo. This global regulator shapes how dimorphic fungal pathogens adapt to the mammalian host, which has broad implications for treating and preventing systemic fungal disease.
通常存在于我们环境中的微生物病原体能够适应并在哺乳动物宿主体内大量繁殖。有六种双态真菌在全球范围内引发疾病，它们在土壤中以非致病性霉菌的形态存在，当孢子被吸入并暴露于高温环境后，会转变为致病性酵母形态。调节这种转变的机制仍不清楚。我们发现一种杂合组氨酸激酶能够感知宿主信号并触发从霉菌形态到酵母形态的转变。该激酶还在体内调节细胞壁完整性、孢子形成以及毒力基因的表达。这种全局调节因子塑造了双态真菌病原体适应哺乳动物宿主的方式，这对治疗和预防系统性真菌疾病具有广泛的意义。
