Secondary metabolites in the interaction of Aspergillus fumigatus and Pseudomonas aeruginosa in cystic fibrosis sputum

Aspergillus fumigatus and Pseudomonas aeruginosa are the most persistent fungal and bacterial pathogens, respectively, commonly co-isolated from the expectorated sputum of cystic fibrosis (CF) patients. Co-colonisation by both microbes has been associated with a worse clinical outcome and a poorer prognosis for CF patients. The recent years have seen multiple attempts at characterising the interactions between the bacterial species and the fungus. While several mechanisms of mutual inhibition have been proposed in published literature, the interaction models have been based on conventional cultivation strategies, and have thus fallen short of appropriately acknowledging the particular nutritional environment, in which the interaction takes place. In the present study, I have developed a model of the interaction that imitates the native conditions of a cystic fibrosis lung more closely. Using the model, which mimics to a certain extent the growth conditions inside the lung, and, at the same time, do not provide a selective advantage to one of the microorganisms over the other, I investigated the behaviour and the secondary metabolism of the microbes. The study led, among others, to the identification of a novel isonitrilated fungal dipeptide alkaloid, as well as a cyanide detoxication mechanism deployed by the fungus in response to bacterial cyanogenesis. Summarily, the results presented here indicate that rather than engaging in extreme antagonistic behaviour, Aspergillus fumigatus and Pseudomonas aeruginosa co-occurring in the human CF lung achieve a delicate balance, detoxifying each other’s secreted secondary metabolic potential.



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