Coinfection with Pseudomonas aeruginosa and Aspergillus fumigatus in cystic fibrosis

Abstract

ObjectivesCystic fibrosis (CF) lung disease is characterised by mucus stasis, chronic infection and inflammation, causing progressive structural lung disease and eventual respiratory failure. CF airways are inhabited by an ecologically diverse polymicrobial environment with vast potential for interspecies interactions, which may be a contributing factor to disease progression. Pseudomonas aeruginosa and Aspergillus fumigatus are the most common bacterial and fungal species present in CF airways respectively and coinfection results in a worse disease phenotype.MethodsIn this review we examine existing expert knowledge of chronic co-infection with P. aeruginosa and A. fumigatus in CF patients. We summarise the mechanisms of interaction and evaluate the clinical and inflammatory impacts of this co-infection.ResultsP. aeruginosa inhibits A. fumigatus through multiple mechanisms: phenazine secretion, iron competition, quorum sensing and through diffusible small molecules. A. fumigatus reciprocates inhibition through gliotoxin release and phenotypic adaptations enabling evasion of P. aeruginosa inhibition. Volatile organic compounds secreted by P. aeruginosa stimulate A. fumigatus growth, while A. fumigatus stimulates P. aeruginosa production of cytotoxic elastase.ConclusionA complex bi-directional relationship exists between P. aeruginosa and A. fumigatus, exhibiting both mutually antagonistic and cooperative facets. Cross-sectional data indicate a worsened disease state in coinfected patients; however, robust longitudinal studies are required to derive causality and to determine whether interspecies interaction contributes to disease progression.

Cystic Fibrosis Clinical Isolates of Aspergillus fumigatus Induce Similar Muco-inflammatory Responses in Primary Airway Epithelial Cells

“…It is possible that strains may vary in other aspects, for example immunological escape from phagocytes [ 38 ], but this is beyond the scope of our epithelial focused study and there is no literature in this regard. Additionally, A. fumigatus strains isolated from adults with CF may display more variable immunostimmulatory capacity as a consequence of prolonged environmental adaptation and interactions with other CF microbes [ 39 ]. The summary for clinicians is that the presence of Aspergillus is more important to early CF lung pathology than the strain of Aspergillus and that typing should remain orientated to antifungal testing, ideally with a broader focus than the current azole testing.…”

Microbiological features of Pseudomonas aeruginosa in children with Cystic Fibrosis

“…For selective isolation of Pseudomonas spp. we used Cetrimide agar with glycerol (BioLife, Italy) [5,9,12]. Salt agar (Farmaktiv, Ukraine) with egg-yolk emulsion (Hi-Media, India) was used for selective isolation of Staphylococcus aureus [13,15].…”

Nitrogen, Iron, and Zinc Acquisition: Key Nutrients to Aspergillus fumigatus Virulence

“…In cystic fibrosis patients, bacteria are predominant, and it has been demonstrated that Pseudomonas aeruginosa uses iron competition to inhibit A. fumigatus growth. In particular, this bacteria produces pyoverdine and pyochelin, iron chelators, and the bacteriophage Pf4, which inhibits fungal metabolism, but its effect could be overcome with ferric ion supplementation [ 91 ].…”