Understanding molecular causes of antifungal resistance in A. fumigatus

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The extent of the problem
Fungal infections affect more than of 1.7 billion people each year, leading to in excess of 1.5 million deaths [1]. More than one third of these are caused by mold infections, predominantly by the major human mold pathogen Aspergillus fumigatus [2]. Chronic pulmonary aspergillosis for instance affects at around 3 million individuals annually resulting in approximately 450, 000 deaths. In contrast, around only 200, 000 individuals suffer from invasive aspergillosis, however, due to its high mortality rate (50% if treated, >99% if untreated) this disease type leads to around 100, 000 deaths a year [2].

The current antifungal arsenal

Fungi are eukaryotes and therefore evolutionarily related to humans, which impedes the development of novel antifungal drugs, because drugs targeting fungal proteins very often target the human ortholog as well [3]. Therefore currently only four classes of antifungal agents are available to treat invasive fungal infections (triazoles, echinocandins, polyenes and nucleobase analogs) and all suffer from drawbacks such as toxicity, drug–drug interactions and poor bioavailability [1]. A. fumigatus’ resistance to triazoles, the major drug class administered for aspergillosis, is emerging rapidly and raises the question whether this class of antifungals can be retained in clinical use [4]. Therefore, novel treatment options are indispensable to combat fungal infections and, simultaneously, tackle the problem of resistance.

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