Neurospora Intermedia As A Rare Cause of Invasive Fungal Infection In Humans

        Neurospora intermedia, an edible filamentous fungus, is commonly used for production of fermented food. This study investigated microbiological and clinical characteristics of four N. intermedia isolates recovered from three patients. The species identification was based on morphology and multi-locus phylogenetic analysis using four genetic loci (28S, Bml, tef-1, and hypothetical protein (NCU02332)). The first patient was a 25-year-old man with chemotherapy-refractory mediastinal germ cell tumor who were intubated due to respiratory failure. N. intermedia was recovered from endotracheal aspirate on the day of intubation and from tissue biopsy of endobronchial mass obtained by bronchoscopic forceps biopsy 3 days later; pathological examination of the biopsy tissue revealed necrotic tissue mixed with many septate fungal hyphae. Both isolates were genetically related and belonged to mating type a. Proven invasive fungal infection presented as tracheobronchitis due to N. intermedia was diagnosed according to the EORTC/MSG definitions. PacBio whole genome sequencing and assembly of the tissue isolate yielded 15 contigs with a genome size of approximately 41.7Mb. The other two isolates were recovered from endotracheal aspirates of two patients with probable invasive pulmonary aspergillosis, respectively, and belonged to mating type A; both patients had high galactomannan (GM) index (Bio-Rad PlateliaTM) (>5) in bronchoalveolar lavage fluid samples but had negative respiratory-tract cultures for Aspergillus during the treatment course. The crude extracts of isolates from three patients cross-reacted with Aspergillus galactomannan antigen testing (GM index >5). All four isolates were susceptible to amphotericin B and voriconazole. In summary, this report first described the recovery of N. intermedia from clinical samples as a rare cause of invasive fungal infection in humans.