The newly nonsporulated characterization of an Aspergillus fumigatus isolate from an immunocompetent patient and its clinic indication

Abstract

Aspergillus fumigatus (A. fumigatus) commonly produces abundant and heavily melanized infectious conidia, which are the primary agents that cause invasive aspergillosis (IA) in immunocompromised patients. We isolated a white nonsporulating A. fumigatus strain (A1j) from an immunocompetent patient. It was identified by histopathological examination and morphological observation, and subsequently confirmed by DNA sequencing of internal transcribed spacer (ITS) regions and partial β-tubulin genes. Neither a long waiting time nor passage on various medium types could stimulate the formation of spores and pigment. No significant relative difference was found in sensitivity to antifungal agents or cell wall destabilizing reagents, as compared to wild-type A. fumigatus Af293. Nevertheless, A1j was hypovirulent in the immunosuppressed mice model, consistent with the good result in our patient. RNA deep-sequencing analysis (RNA-seq) revealed that hundreds of transcripts were significantly dysregulated, including those related to pigmentation and sporulation. qRT–PCR confirmed the anergic state of key regulator brlA for sporulation under the induction of conidiation conditions, but without mutation. To the best of our knowledge, this is the first report of a white, nonsporulating A. fumigatus strain infection in an immunocompetent patient. In our opinion, A1j may represent a mutant of typical A. fumigatus, providing a new clue for identification of clinical A. fumigatus isolates. Furthermore, the good prognosis of our patient and the reduced virulence in the mice model infected with A1j highlight the potential of sporulation inhibitors as a new generation of antifungal agents.