New cell wall targets for antifungal drugs.

Fungal infections in humans caused by filamentous moulds and yeasts continue to be serious and often life-threatening, especially among immunocompromised patients. One of the most immediate and unmet medical needs is the identification of new treatment options for invasive aspergillosis infection. The fungal cell wall, as the most obvious difference between human and fungal cells, represents an excellent target for antifungals. Cell wall carbohydrates are polymerized from uridine di-phospho sugars that are synthesized by several biochemical pathways. The pathways for the synthesis of these cell wall precursors represent unexplored targets for new antifungals that have modes of action that are different from currently used therapeutics. This review will focus on the identification of several new therapy targets and on assays to screen for inhibitors of enzymes critical to the synthesis of cell wall precursors.