Powering up antifungal treatment: using small molecules to unlock the potential of existing therapies

• Published in: mBio 2023-08, Vol.14 (4), p.e0107323-e0107323
• Main Authors: Shapiro, Rebecca S, Gerstein, Aleeza C
• Format: Article
• Language: English
• Subjects: antifungal resistance; antifungal therapy; antimicrobial combinations; drug screening; mycology
• ISSN: 2150-7511; 2150-7511
• DOI: 10.1128/mbio.01073-23

Fungal pathogens are increasingly appreciated as a significant infectious disease challenge. Compared to bacteria, fungal cells are more closely related to human cells, and few classes of antifungal drugs are available. Combination therapy offers a potential solution to reduce the likelihood of resistance acquisition and extend the lifespan of existing antifungals. There has been recent interest in combining first-line drugs with small-molecule adjuvants. In a recent article, Alabi et al. identified 1,4-benzodiazepines as promising molecules to enhance azole activity in pathogenic spp. (P. E. Alabi, C. Gautier, T. P. Murphy, X. Gu, M. Lepas, V. Aimanianda, J. K. Sello, I. V. Ene, 2023, mBio https://doi.org/10.1128/mbio.00479-23). These molecules have no antifungal activity on their own but exhibited significant potentiation of fluconazole in azole-susceptible and -resistant isolates. Additionally, the 1,4-benzodiazepines increased the fungicidal activity of azoles that are typically fungistatic to spp., inhibited filamentation (a virulence-associated trait), and accordingly increased host survival in . This research thus provides another encouraging step on the critical pathway toward reducing mortality due to antimicrobial resistance.