The Aspergillus fumigatus Secretome Alters the Proteome of Pseudomonas aeruginosa to Stimulate Bacterial Growth: Implications for Co-infection

Abstract

Individuals with cystic fibrosis are susceptible to co-infection by Aspergillus fumigatus and Pseudomonas aeruginosa. Despite the persistence of A. fumigatus in the cystic fibrosis lung P. aeruginosa eventually predominates as the primary pathogen. Several factors are likely to facilitate P. aeruginosa colonization in the airways, including alterations to the microbial environment. The cystic fibrosis airways are hypoxic, nitrate-rich environment, and the sputum has higher amino acid concentrations than normal. In this study, significant growth proliferation was observed in P. aeruginosa when the bacteria were exposed to A. fumigatus culture filtrates (CuF) containing a high nitrate content. Proteomic analysis of the A. fumigatus CuF identified a significant number of environment-altering proteases and peptidases. The molecular mechanisms promoting bacterial growth were investigated using Label-free quantitative (LFQ) proteomics to compare the proteome of P. aeruginosa grown in the A. fumigatus CuF and in CuF produced by a P. aeruginosa-A. fumigatus Co-culture, to that cultured in P. aeruginosa CuF. LFQ proteomics revealed distinct changes in the proteome of P. aeruginosa when cultured in the different CuF, including increases in the levels of proteins involved in denitrification, stress response, replication, amino acid metabolism and efflux pumps, and a downregulation of pathways involving ABC transporters. These findings offer novel insights into the complex dynamics that exist between P. aeruginosa and A. fumigatus. Understanding the molecular strategies that enable P. aeruginosa to predominate in an environment where A. fumigatus exists is important in the context of therapeutic development to target this pathogen.

Let’s Get Physical: Bacterial-Fungal Interactions and Their Consequences in Agriculture and Health

“…While there is an emphasis on the inhibition of A. fumigatus by P. aeruginosa , in the study by Briard et al, it was found that some bacterial volatile compounds could actually stimulate fungal growth [ 47 ]. Recently, a study reported that the secretome of A. fumigatus stimulates bacterial growth by altering the P. aeruginosa proteome [ 48 ].…”

“…Numerous reports of MHB isolation, identification, and studies on their consequences exist [ 49 , 50 , 51 , 52 , 53 ]. The roles of MHB in symbiosis, their effects on arbuscular mycorrhizal or ectomycorrhizal host, and their specificities and mechanisms have been studied for decades and have been reviewed extensively elsewhere [ 46 , 47 , 48 ]. Such tri-partite interactions help promote plant growth as well as stress tolerance [ 47 , 54 , 55 , 56 ].…”

Bacterial Interactions with Aspergillus fumigatus in the Immunocompromised Lung

“…For example, P. aeruginosa can inhibit the growth of A. fumigatus conidia, but not of preformed hyphae [ 17 ]. This may be attributed to the ability of hyphae, but not conidia to produce gliotoxin which has anti- Pseudomonas activity [ 100 , 113 ]. A. fumigatus produce hydroxamate-containing siderophores (ferricrocin, hydroxyferricrocin, fusarinine C, triacetylfusarinine C) in response to iron limitation.…”

“…How these enzymes directly or indirectly influence bacterial growth has not yet been investigated in detail, however, recent studies have shown that A. fumigatus alters the environmental conditions in vitro, by converting a nutrient-poor, nitrate-rich environment into one rich in amino acids. These conditions, known to exist in the CF airways, may enable P. aeruginosa to outcompete A. fumigatus by promoting a metabolic-driven increase in bacterial growth [ 113 ]. Analysis of the culture filtrates produced by A. fumigatus identified an abundance of degradative enzymes which are also involved in virulence, including alkaline protease 1, alkaline protease 2, aspergillopepsin-1, and major allergen Asp f 2 [ 115 , 117 , 118 , 119 ].…”

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

“…A. fumigatus response to iron is also modulated by a pseudomonal quorum sensing molecule, P. aeruginosa quinolone signal, which enhances fungal growth and metabolism under iron-rich conditions, similar to those found in the CF lung environment [ 138 ]. Conversely, recent proteomic analysis by Margalit et al has shown that A. fumigatus can confer fitness to P. aeruginosa by increasing environmental nutrient availability, especially of amino acids and nitrate, which thereby stimulates bacterial growth and pathogenicity [ 139 ]. The nature of A. fumigatus-P. aeruginosa interactions becomes more complicated when other factors are considered.…”