HOW ASPERGILLUS INVADES THE RESPIRATORY EPITHELIUM

Elaine Bignell

Abstract: 

Destruction of the pulmonary epithelium is a major feature of lung diseases caused by the mould pathogen 
Aspergillus fumigatus. Although it is widely postulated that tissue invasion is governed by fungal proteases, 
A. fumigatus mutants lacking individual or multiple enzymes remain fully invasive, suggesting a concomitant 
requirement for other pathogenic activities during host invasion. In favour of the view that tissue invasion 
is a genetically regulated trait, we recently described a tissue non-invasive A. fumigatus phenotype in 
a mutant lacking the pH-responsive transcription factor PacC. PacC null mutants are defective in both 
contact-mediated epithelial entry and protease and gliotoxin expression, and significantly attenuated for 
pathogenicity in leukopenic mice. We exploited this phenotype as a tool to dissect the mechanistic basis of 
invasive growth. Our study reveals a combinatorial mode of tissue entry dependent upon sequential, and 
mechanistically distinct, perturbations of the pulmonary epithelium and demonstrates, for the first time a 
protective role for Dectin-1 blockade in epithelial defences. 

2016

Full conference title: 

7th Advances Against Aspergillosis