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

世界卫生组织（who）最近公布了一份名单，列出了19种严重、高度和中度优先的真菌病原体，它们每年造成的死亡人数总和超过了疟疾、结核病、艾滋病、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人类相似，所以抗真菌抗生素的灵丹妙药很少。耐药真菌也是一个致命的、正在加速的全球性问题。新药目前正在临床试验中，了解这些新的抗真菌药物在患者身上的效果是至关重要的。这个项目解决了我们知识上的一个空白，即如果真菌没有被药物完全杀死，暴露于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个关键问题。学生将建立真菌的结构是如何通过药物暴露而改变的，以及药物修饰真菌细胞诱导的免疫反应的后果。这一新知识将为未来抗真菌药物管理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.