Dataset Information

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, however 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. In this study, significant growth proliferation was observed in P. aeruginosa when the bacteria were exposed to culture filtrates produced by A. fumigatus in a nitrate-rich, nutrient-poor liquid broth, Czapek-Dox. Proteomic analysis of the A. fumigatus culture filtrate identified a significant number of environment-altering proteases and peptidases, which may contribute to the growth promoting effect observed when P. aeruginosa is exposed to this culture filtrate. These findings offer insights into the determinants that contribute to P. aeruginosa proliferation in the presence of A. fumigatus.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Aspergillus Fumigatus Af293

SUBMITTER: James Carolan

LAB HEAD: Jim Carolan

PROVIDER: PXD018112 | Pride | 2020-07-22

REPOSITORIES: Pride

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			Action	DRS
	AM_A.msf	Msf
	AM_A.raw	Raw

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Publications

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

Margalit Anatte A Carolan James C JC Sheehan David D Kavanagh Kevin K

Molecular & cellular proteomics : MCP 20200523 8

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 environments, and the sputu ...[more]

PMID: 32447284

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Project description:The airways of cystic fibrosis patients are chronically colonized by a diverse range of microbial pathogens, the composition of which changes throughout life Alteration to the pulmonary environment caused by inter-microbial interactions and pathogen-host interactions influence the type of microbes that can engage in sustained infection. The opportunistic bacterial pathogen Pseudomonas aeruginosa is the primary cause of morbidity and mortality amongst individuals with cystic fibrosis and it is estimated that 60 – 80 % of cystic fibrosis patients experience chronic P. aeruginosa infection by the age of 20 years Aspergillus fumigatus is the most prevalent fungal pathogen isolated from cystic fibrosis airways, affecting up to 58% of patients. It is the causative agent of allergic bronchopulmonary aspergillosis (ABPA), a hypersensitivity disorder resulting from the inhalation of fungal conidia. Although co-colonization of the cystic fibrosis airways by P. aeruginosa and A. fumigatus is rare (3.1 – 15.8 %) disease prognosis is poor when both are present. However, sequential infection is more common. It has recently been suggested that A. fumigatus is more prevalent in juvenile cystic fibrosis patients that has been initially reported due to inconsistencies in the culture methods used to detect A. fumigatus. Despite the prevalence and persistence of A. fumigatus, P. aeruginosa predominates as the primary pathogen in the cystic fibrosis lung, suggesting that interactions with other pathogens such as A. fumigatus may influence the pathogenicity of P. aeruginosa by altering its virulence. We report here an investigation of the effect of culturing P. aeruginosa in the presence of A. fumigatus by measuring differences in growth rate and the overall proteome of the bacteria. It was hypothesized that A. fumigatus creates an environment that promotes a metabolic-driven increase in P. aeruginosa that results in it outcompeting the fungus. The molecular basis of this increased proliferation was investigated further using Label-free quantitative (LFQ) proteomics to characterise the proteome changes in P. aeruginosa when exposed to the supernatant of i) A. fumigatus alone ii) the supernatant of an A. fumigatus/P. aeruginosa co-culture and iii) P. aeruginosa alone. LFQ proteomics involves the simultaneous identification and quantification of thousands of proteins (the ultimate determinants of phenotype) from a single sample has recently been employed to characterise the P. aeruginosa proteome in response to iron limiting conditions, resolving how how the bacteria survives and proliferates in such environments.

Project description:Aspergillus fumigatus is an opportunistic fungal pathogen of the lungs resulting in both chronic and acute infection. The fungus interacts with numerous bacteria that compose the microflora of the lung including Pseudomonas aeruginosa and Klebsiella pneumoniae, both common isolates from Cystic fibrosis sputum. It is well documented that bacterial and fungal interactions both physically and through production of secreted products which can alter the growth and virulence of other species. The interaction with P. aeruginosa has been characterised previously indicating decreased growth and increased gliotoxin production in the presence of cells and the opposite when only exposed to culture filtrate. In our analysis exposure of cell free culture filtrate inhibited fungal growth and increased gliotoxin production. This was supported with proteomic analysis indicating reduction in 1,3-beta-glucanosyltransferase (-3.97 fold), methyl sterol monooxygenase erg25B (-2.9 fold) and Calcium/calmodulin dependent protein kinase (-4.2 fold) involved in fungal development. Coupled with increased expression of Glutathione S-transferase gliG (6.17 fold), non-ribosomal peptide synthase gliP (3.67 fold), O-methyltransferase gliM (3.5 fold), Gamma-glutamyl acyltransferase gliK (2.89 fold) and thioredoxin reductase gliT (2.33 fold) involved in Gliotoxin production indicate a possible shift towards secondary metabolism. Qualitative proteomic analysis of the bacterial supernatant also elucidates possible mechanisms for these alterations including physical interaction by Outer membrane protein A, High-affinity zinc uptake system protein ZnuA and Iron uptake system component EfeO reducing essential nutrient availability, enzymatic activity including Periplasmic serine endoprotease DegP-like and redox active proteins including Alkyl hydroperoxide reductase C. These proteomic alterations to the fungus could have implications for the severity of virulence in the context of coinfection and may impact disease progression.

Dataset Information

The Aspergillus fumigatus secretome alters the proteome of Pseudomonas aeruginosa to stimulate bacterial growth: implications for co-infection

Dataset's files

Publications

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

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