How to bolster the antifungal pipeline

Abstract

Few drugs are coming to market, but opportunities for drug development exist

Exploiting mitochondria as targets for the development of new antifungals

“…43 A characteristic of many of these antifungals is that they inhibit targets not of the current vintage of antifungals. Of importance, one of the preclinical compounds is a mitochondrial inhibitor.…”

“…Five categories of currently used or new antifungal drugs have been described. 43 Each category of drugs is licensed for: 1) systemic treatment, 2) superficial treatment, 3) in clinical trials, 4) no longer in development, or no reports since 2012, and 5) in preclinical development. 43 Category #1 and #2 compounds are those that we are most familiar (triazoles, echinocandins, and amphotericin B), and those remodeled from each category.…”

“…43 Each category of drugs is licensed for: 1) systemic treatment, 2) superficial treatment, 3) in clinical trials, 4) no longer in development, or no reports since 2012, and 5) in preclinical development. 43 Category #1 and #2 compounds are those that we are most familiar (triazoles, echinocandins, and amphotericin B), and those remodeled from each category. A total of 26 new compounds are listed in categories #3-5, but 14 of those belong in category #4, which as stated above, have apparently not advanced in the clinical pipeline.…”

When green and red mycology meet: Impressions from an interdisciplinary forum on virulence mechanisms of phyto- and human-pathogenic fungi

“…8 This development is accompanied by a diagnostic as well as therapeutic dilemma: fungal infections are often underdiagnosed and may then be treated rather late and unsatisfactorily with only a limited set of antimycotics available. 3,9 With the pharmaceutical pipeline lagging behind the demand for novel antifungal substances, 10 accompanied by emerging resistance against some of the most established compounds, such as azoles, 11 the need for novel starting points in antifungal therapy is evident and urgent. One key aspect in the identification of such targets lies in the comprehensive understanding of the pathogenesis of fungal infections.…”

Competition ofCandida glabrataagainstLactobacillusis Hog1 dependent

“…It is estimated that each year, 1.5 to 2 million people worldwide die of a fungal infection (Denning et al, 2015) and that about 10% of all bloodstream infections in the United States are caused by fungi (Wisplinghoff et al, 2004). Several Candida species are intimately connected to humans as they are a part of the human microbiome and appear both as commensals (e.g., in the gut) and pathogens (Huffnagle et al, 2013).…”