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

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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.