Regulation of secretion of the fungal virulence determinant, phospholipase B

在过去的几年里，由真菌引起的严重系统性感染急剧增加，特别是在免疫系统功能不佳的人中。这些疾病的治疗是有问题的，因为现有的少数几种药物不是非常有效，而且-或者会造成显著的副作用。人们对真菌如何致病知之甚少，如果要控制这些感染，这个问题必须得到解决。我们已经发现，磷脂酶B(PLB)是由致病真菌新生隐球菌分泌的，它在使真菌能够入侵宿主细胞并从肺部传播到大脑中起重要作用，在那里它可以引起脑膜脑炎。PLB也是由其他致病真菌产生的。PLB的分泌机制完全未知。在这个项目中，我们的目标是确定参与PLB分泌的途径，目的是开发致病真菌特有的步骤，为未来设计新的抗真菌药物。

Serious systemic infections due to fungi have increased dramatically in the past few years, especially in people with poorly functioning immune systems. Treatment of these conditions is problematic because the few drugs which are available are not highly effective, and-or cause significant side-effects. Little is understood of how fungi cause disease, and this problem must be addressed if these infections are to be contained. We have discovered that the enzyme, phospholipase B (PLB), is secreted by the disease-causing fungus, Cryptococcus neoformans, and that it is important in enabling the fungus to invade the host's cells and spread around the body from the lungs to the brain, where it can cause meningoencephalitis. PLB is also produced by other disease-causing fungi. The mechanism of PLB secretion is completely unknown. In this project we aim to determine the pathways involved in PLB secretion with the intention of exploiting steps unique to pathogenic fungi, for the future design of new anti-fungal drugs.