Lung colonization by Aspergillus fumigatus is controlled by ZNF77

Sara Gago, Nicola Overton, Nagwa Ben Ghazzi, Lily Novak Frazer, Nick Read, D W Denning, Paul Bowyer

Research output: Contribution to journalArticlepeer-review


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.
Original languageEnglish
Article number3835
JournalNature Communications
Publication statusPublished - 20 Sept 2018

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre


Dive into the research topics of 'Lung colonization by Aspergillus fumigatus is controlled by ZNF77'. Together they form a unique fingerprint.

Cite this