Mandimycin: A phospholipid-targeting natural polyene macrolide overcoming multidrug resistance in invasive fungal infections

Developing novel anti-infective drugs is essential to combat antimicrobial resistance, address emerging pathogens, and safeguard global health against evolving infectious threats. A recent publication in the esteemed journal Nature by Qisen Deng et al. reported on the comprehensive evaluation of the therapeutic efficacy of mandimycin against multidrug-resistant (MDR) fungal pathogens. The polyene macrolide antifungal antibiotic, mandimycin, was discovered using a phylogeny-guided natural-product discovery platform. Authors utilized various in vivo mouse models such as systemic and soft-tissue infections to assess the antifungal activity of mandimycin. The efficacy was measured by quantifying the fungal burden in major organs and assessing survival rates. In systemic infections, mandimycin demonstrated significant dose-dependent antifungal efficacy, as compared to amphotericin B, particularly in cases where the latter was ineffective against MDR C. auris . Furthermore, mandimycin showed a favorable safety profile, with low toxicity and no observed side effects at effective doses. The study's findings contribute valuable insights into the potential of mandimycin as a novel antifungal agent, offering hope for improved treatment options against challenging fungal infections. The results pave the way for further research and clinical applications in the fight against antifungal resistance. • Mandimycin, a polyene macrolide was discovered from phylogeny-guided natural product discovery platform. • Mandimycin was reported to bind on multiple sites on the phospholipid in the fungal cell memberane. • Mandimycin demonstrated potent fungicidal effects against MDR fungal pathogens in mouse infection models.