Exposure of Aspergillus fumigatus to Klebsiella pneumoniae culture filtrate inhibits growth and stimulates gliotoxin production.
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ABSTRACT: 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.
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Aspergillus Fumigatus Af293
SUBMITTER: Aaron Curtis
LAB HEAD: Professor Kevin Kavanagh
PROVIDER: PXD037833 | Pride | 2023-03-11
REPOSITORIES: Pride
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