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    Lung colonization by Aspergillus fumigatus is controlled by ZNF77.

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    Authors
    Gago, S
    Overton, Nicola L D
    Ben-Ghazzi, N
    Novak-Frazer, L
    Read, N
    Denning, D
    Bowyer, P
    Affiliation
    Manchester Fungal Infection Group, Division of Infection, Immunity and Respiratory Medicine, University of Manchester, CTF Building, 46 Grafton Street, Manchester, M13 9NT
    Issue Date
    2018-09-20
    
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    Show full item record
    Abstract
    Aspergillus fumigatus is a critical pathogen of humans. Exposure to A. fumigatus conidia occurs frequently but is normally cleared from the respiratory airways. In contrast, individuals with respiratory diseases are often highly colonized by fungi. Here, we use genome-edited epithelial cells to show that the genetic variant rs35699176 in ZNF77 causes loss of integrity of the bronchial epithelium and increases levels of extracellular matrix proteins. These changes promote A. fumigatus conidial adhesion, germination and growth. RNA-seq and LC/MS-MS analysis reveal rs35699176 upregulates vesicle trafficking leading to an increment of adhesion proteins. These changes make cells carrying rs35699176 more receptive to A. fumigatus in the early stages of infection. Moreover, patients with fungal asthma carrying rs35699176+/- have higher A. fumigatus loads in their respiratory airway. Our results indicate ZNF77 as a key controller of Aspergillus colonization and suggest its utility as a risk-marker for patient stratification.
    Citation
    Lung colonization by Aspergillus fumigatus is controlled by ZNF77. 2018, 9(1): 3835 Nat Commun
    Journal
    Nature Communications
    URI
    http://hdl.handle.net/10541/621292
    DOI
    10.1038/s41467-018-06148-7
    PubMed ID
    30237437
    Type
    Article
    Language
    en
    ISSN
    2041-1723
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41467-018-06148-7
    Scopus Count
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    All Paterson Institute for Cancer Research

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