Innovative Antifungal Drug

AAAS: “Deadly fungi are becoming drug-resistant. A new compound could beat them.” Multi-drug-resistant bacteria get lots of attention, but some fungal organisms also pose a critical threat to global health. Now, researchers have found a compound that seems to kill fungi in an entirely new way. “Many of the drugs used to fight off bacterial or fungal infections come from the microbial world themselves: They’re based on compounds that microorganisms have developed to kill each other.” The agent ampotericin B evolved in the bacterium Streptomyces nodosus to protect itself from fungi, but in treatment of human fungal infections “amphoterrible” has multiple toxicities. Researchers led by microbiologist Zongqiang Wang at the State Key Laboratory of Natural Medicines mined a database of more than 300,000 bacterial genomes, built a family tree of the genes involved in polyene production, and identified gene clusters that seemed to have diverged over time. One of these clusters, in the bacterium Streptomyces netropsis, encoded for a substance they named mandimycin, after Wang’s daughter, whose name [in Romanized spelling] is Mandi. Unlike other polyenes, mandimycin does not attack the cholesterol-like ergosterol — rather membrane phospholipids — another basic building block of fungal cells. Early data in a mouse model show activity against 3 serious infections. The first is Candida albicans, which causes vaginal yeast infections but also more serious invasive disease. The second is Candida auris, a yeast that emerged as a deadly threat resistant to all major drugs classes and especially difficult to eradicate in the hospital setting. The third is Cryptococcus neoformans, a fungus that kills more than 100,000 people living with HIV every year. Critically, the new agent may be less toxic to the kidneys than amphotericin B. And mandimycin could possibly be formulated as an oral rather than IV medication. Count me skeptical per usual, as we have no human data on safety + effectiveness yet.