The immunological consequences of antifungal drug exposure: supporting clinical regimens for the treatment of invasive fungal infection

世界卫生组织最近公布了19种关键、高度和中等优先的真菌病原体的名单，这些病原体每年导致的死亡人数超过疟疾、结核病、艾滋病毒、乳腺癌和前列腺癌。目前还没有针对真菌的保护性疫苗，而且由于真菌的生物化学在许多方面与我们自己的相似，神奇的子弹抗真菌抗生素很稀缺。耐药真菌也是一个致命的、正在加速的全球问题。新药现在正在临床流水线中，了解这些新的抗真菌药物在患者身上的表现是至关重要的。这个项目解决了我们知识中的一个缺口，即如果真菌不能被药物彻底杀死，那么接触这些药物是否会损害免疫系统帮助清除感染的能力。我们有丰富的内部经验来回答这一关键问题。学生将确定药物暴露如何改变真菌的结构，以及药物修饰的真菌细胞诱导的免疫反应的后果是什么。这一新知识将为未来有关抗真菌药物使用的临床决策提供信息。

The World Health Organisation recently published a list of 19 critical, high and medium priority species of fungal pathogens that collectively cause more annual deaths than malaria, TB, HIV, breast and prostate cancer. There are no protective vaccines against fungi, and because the biochemistry of fungi is in many ways similar to our own, magic bullet antifungal antibiotics are scarce. Drug resistant fungi are also a deadly and accelerating global problem. New drugs are now in the clinical pipeline and it is essential to understand how well these new antifungals will perform in patients. A gap in our knowledge is addressed in this project, which is to find out whether exposure to these drugs will compromise the ability of the immune system to help clear an infection if the fungus is not killed outright by the drug. We have considerable in-house experience to answer this critical question. The student will establish how the structure of the fungus is changed by drug exposure and what the consequences are to the immune response that is induced by the drug-modified fungal cell. This new knowledge will inform clinical decision making in the future about antifungal drug administration.