Production of ETP-Type (Epipolythiodioxopiperazine) Mycotoxins in Clinical Fungal Isolates

Gliotoxin, an epipolythiodioxopiperazine (ETP) toxin, has been reported in several fungal species, but its distribution remains unclear. We analyzed 140 clinical isolates from two major hospitals using HPLC and LC–MS/MS to assess gliotoxin production. Gliotoxin was detected only in Aspergillus fumigatus isolates, with no production observed in any other species under multiple culture conditions. Molecular networking and comparative genomics revealed distinct ETP-related pathways in non- A. fumigatus species, including aspirochlorine derivatives in Aspergillus flavus and aranotin-related metabolites in Aspergillus terreus . These findings clarify species-specific ETP profiles and confirm A. fumigatus as the sole gliotoxin producer among the isolates examined.