Factoring in the Complexity of the Cystic Fibrosis Lung to Understand Aspergillus fumigatus and Pseudomonas aeruginosa Interactions

Abstract

Pseudomonas aeruginosa has long been established as the most prevalent respiratory pathogen in Cystic Fibrosis (CF) patients, with opportunistic infection causing profound morbidity and mortality. Recently, Aspergillus fumigatus has also been recognised as a key contributor to CF lung deterioration, being consistently associated with decreased lung function and worsened prognosis in these patients. As clinical evidence for the common occurrence of combined infection with these two pathogens increases, research into the mechanism and consequences of their interaction is becoming more relevant. Clinical evidence suggests a synergistic effect of combined infection, which translates into a poorer prognosis for the patients. In vitro results from the laboratory have identified a variety of possible synergistic and antagonistic interactions between A. fumigatus and P. aeruginosa. Here, we present a comprehensive overview of the complex environment of the CF lung and discuss how it needs to be considered to determine the exact molecular interactions that A. fumigatus and P. aeruginosa undergo during combined infection and their effects on the host.

Keywords: Aspergillus fumigatus; Pseudomonas aeruginosa; combined infection; cystic fibrosis.

Figure 1

Pseudomonas aeruginosa-Aspergillus fumigatus interactions identified in different models of combined infection. The figure summarises the type of interaction and the main effects observed in published studies to-date, which are divided based on the level of complexity of the model. In vitro studies have detected predominantly antagonistic interactions of one pathogen on the other (red arrow), but a few have also described synergistic interactions (green arrows). All other models have detected increased (black arrows) pathogen burden and/or mortality and clinical studies have detected decreased lung function.