Building a Global Innovation Pipeline for Organometallic Antifungals Against Nakaseomyces glabratus: Correspondence on Maqueda-Cabrera and Cuéllar-Cruz.

Abstract

Maqueda-Cabrera and Cuéllar-Cruz reported dose-dependent activity of the organometallic compound N-(2-hydroxyethyl)ferroceneselenoamide (FE1) against Nakaseomyces glabratus in a Galleria mellonella infection model. FE1 at 20 mg/kg produced complete larval protection and reduced fungal burden relative to fluconazole tested at the same dose. These findings are promising but remain preliminary because only the reference strain CBS138 was evaluated and the compound's mechanism of action is unknown. Further work should test geographically and genetically diverse clinical isolates, azole- and echinocandin-resistant phenotypes, and other clinically important opportunistic yeasts. Mechanistic studies should examine fungal stress-response pathways, resistance evolution, toxicity, pharmacokinetics/pharmacodynamics, and larval immune responses. G. mellonella is best positioned as a pre-screening or intermediate-screening experimental model rather than a direct predictor of clinical efficacy. A staged programme that links reproducible invertebrate endpoints to mammalian validation and WHO fungal-priority objectives could clarify whether FE1 merits further development as an antifungal candidate.