Aspergillus fumigatus: virulence genes in a street-smart mold

Abstract

Infections with the filamentous fungus Aspergillus fumigatus are among the most devastating of the systemic mycoses. Unlike most primary pathogens, which possess virulence traits that developed in association with a host organism, evidence suggests that the virulence of A. fumigatus entails a collection of 'street-smart' attributes that have evolved to resist the adverse selection pressures encountered in decaying vegetation. These features enhance the overall competitiveness of the organism in its environmental niche but are also thought to promote growth and survival in a human host. Although many of the genes that are responsible for these characteristics do not fit into the classical definition of a virulence factor, they are nonetheless important to the pathogenesis of aspergillosis and may therefore provide novel opportunities for antifungal development.

Fig. 1

Schematic illustration of the pathogenesis of invasive aspergillosis (not drawn to scale). A. fumigatus conidia are small enough (2-3 µm in diameter) to reach the distal airways when inhaled (left). A cross section of the alveolar space is enlarged in the center panel, showing the close proximity of adjacent blood vessels in the interalveolar septum. In a susceptible host, the conidia are able to germinate and damage the blood-air interface. This barrier is comprised of a surfactant layer (blue), a type I pulmonary epithelial cell (pink), and an underlying microvascular endothelial cell (red). Loose interstitial tissue can sometimes be found between the epithelial and endothelial cells, but when the two cells are closely apposed the basal laminae fuse (green), making the barrier only 0.1 – 1.5 µm in thickness. The growing hyphae eventually penetrate this barrier and hyphal fragments are released into the blood, providing access to other organs by extravascular invasion (right panel).