The molecular basis of invasive growth in the pathogenic mould Aspergillus fumigatus

Elaine Bignell

Author address: 

Institute of Inflammation and Repair, The University of Manchester, UK


In lung diseases caused by the mould Aspergillus fumigatus epithelial destruction is thought to be mediated by proteases of fungal origin. We have found that the A. fumigatus pH-responsive transcription factor PacC governs expression of secreted proteases during invasive lung infections and is required for epithelial invasion and pathogenicity. In- and ex-vivo analyses of infected epithelia revealed that A. fumigatus elicits a series of distinct, and sequentially implemented assaults upon epithelial integrity, consisting of (I) epithelial entry (II) cell wall-mediated epithelial disaggregation and (III) protease-mediated damage, all of which are deficient in the ΔpacC mutant. Though damaging, internalisation of A. fumigatus spores by alveolar epithelial cells was found, via nystatin protection assays, to promote fungal clearance. Concordantly, spores of the ΔpacC mutant persisted in the lungs of leukopenic mice. Aberrant remodelling of the ΔpacC cell wall during initiation of mammalian infection suggested the β-glucan receptor, Dectin-1, as mediating spore internalisation, a hypothesis which was proven by the anti-internaisation activity of an anti-Dectin 1 antibody in vitro. Consistent with a curative role for spore internalisation, pulmonary damage was heightened in leukopenic Dectin-1–/–mice relative to wild type counterparts. Our findings shift the pathophysiological profile of this everyday host-pathogen interaction to one in which neutrophil titre presents a risk which is secondary to competence of epithelial defences, and sets a new precedent for the unified study of the diverse pulmonary complications caused by A. fumigatus


abstract No: 


Full conference title: 

Microbiology Society Annual Conference
    • MS 2013