title: 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.
authors.affiliation: Department of Dermatology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Dermatology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Qingtao
authors.initials: Q
authors.lastname: Kong
authors.affiliation: Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Microbiology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Cai
authors.affiliation: Department of Dermatology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Dermatology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
authors.forename: Peiying
authors.initials: P
authors.lastname: Chen
authors.affiliation: Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Microbiology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Jinxing
authors.initials: J
authors.lastname: Song
authors.affiliation: Jiangsu Key Laboratory for Microbes and Functional Genomics, Jiangsu Engineering and Technology Research Center for Microbiology, College of Life Sciences, Nanjing Normal University, Nanjing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lu
authors.affiliation: Department of Dermatology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China; Department of Dermatology, Jinling Hospital, Southern Medical University, Guangzhou, China. Electronic address: sanghong@nju.edu.cn.
authors.forename: Hong
authors.initials: H
authors.lastname: Sang
mesh_terms: D000818:Animals; D001228:Aspergillosis / Q000382:microbiology* / Q000473:pathology*; D001232:Aspergillus fumigatus / Q000235:genetics / Q000254:growth & development* / Q000302:isolation & purification; D004271:DNA, Fungal / Q000737:chemistry / Q000235:genetics; D021903:DNA, Ribosomal Spacer / Q000737:chemistry / Q000235:genetics; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D051379:Mice; D009154:Mutation; D010860:Pigments, Biological / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D013172:Spores, Fungal / Q000254:growth & development*; D014404:Tubulin / Q000235:genetics; D014774:Virulence
chemical_list: D004271:DNA, Fungal; D021903:DNA, Ribosomal Spacer; D010860:Pigments, Biological; D014404:Tubulin
keywords: Aspergillus fumigatus; Characterization; Clinic indication; Identification; Melanin; Sporulation