A marine microbiome antifungal targets urgent-threat drug-resistant fungi

Abstract

New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant Candida auris. Leveraging the microbiomes of marine animals and cutting-edge metabolomics and genomic tools, we identified encouraging lead antifungal molecules with in vivo efficacy. The most promising lead, turbinmicin, displays potent in vitro and mouse-model efficacy toward multiple-drug–resistant fungal pathogens, exhibits a wide safety index, and functions through a fungal-specific mode of action, targeting Sec14 of the vesicular trafficking pathway. The efficacy, safety, and mode of action distinct from other antifungal drugs make turbinmicin a highly promising antifungal drug lead to help address devastating global fungal pathogens such as C. auris.

Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris

“…Turbinmicin revealed as a promising anti-biofilm and antifungal drug [140]. vesicular trafficking pathway [138]. Moreover, the same team rep of turbinmicin to block biofilm formation.…”

“…In 2020, Zhang et al reported the identification of turbinmicin, a lead antifungal which was identified from marine microbiome ( Figure 25 ). Turbinmicin is highly interesting because it functions through a fungal-specific mode of action, targeting Sec14 of the vesicular trafficking pathway [ 138 ]. Moreover, the same team reported the striking ability of turbinmicin to block biofilm formation.…”

Turbinmicin inhibits Candida biofilm growth by disrupting fungal vesicle–mediated trafficking

“…We have reported that Candida biofilm extracellular matrix components critical for biofilm cell drug resistance are delivered by extracellular vesicles (EVs) (12)(13)(14). The recent discovery of molecules produced by the microbiome of a marine animal identified turbinmicin as an antifungal that targets the vesicle delivery pathway (15). We hypothesized that this therapeutic would subvert the protection afforded by the vesicle-delivered biofilm matrix.…”

Combining chemogenomic and gene-dose assays to investigate drug synergy

“…At present, the available therapies, particularly for invasive infections, are limited to four categories of antifungal drugs; azoles, polyenes, echinocandins, and 5-flucytosine 7 , and the clinical results from most IFI cases are not optimal. In addition, emerging pathogens resistant to common antifungals 8 such as the pan drug-resistant yeast Candida auris have spread in health care facilities globally 9,10 . One potential solution to the dearth of effective treatments is to explore the antifungal efficacy of novel drug combinations, including those prescribed for diverse indications 11 .…”