Fig. 5: Schematic overview of the main strategies employed by A. fumigatus in response to the interaction with K. pneumoniae.

Glucose starvation and inhibitory molecule production due to overgrowth of K. pneumoniae activates the catabolism of fatty acids as a source of acetyl-CoA supply. As a consequence, beta-oxidation and the glyoxylate cycle are induced, feeding the TCA cycle and keeping it activated. In parallel, the GABA shunt is also activated. The amino acid sources in the milieu are taken up by fungal cells and are transferred into the methionine and cysteine metabolism. The by-products can regulate ethanol production, which also supplies acetyl-CoA units to the TCA cycle. Methionine and cysteine metabolism can control amino acid production, regulate translation kinetics, enhance oxidative protection and boost gliotoxin production. Red letters indicate induced genes/proteins, products and processes, while purple letters reflect low-level induction. The translation deregulated process is indicated in blue letters. Dashed arrows reflect acetyl-CoA transport between cellular compartments.