Bacterial membrane vesicles of Pseudomonas aeruginosa activate adenosine monophosphate-activated protein kinase signaling through inhibition of mitochondrial complex III.

Bacterial membrane vesicles (BMVs) are secreted by many pathogenic bacteria and known to stimulate various host responses upon infection, thereby contributing to the pathogenicity of bacterial pathogens like Pseudomonas aeruginosa. While the effects of BMVs on host immune responses are well studied, little is known about their impact on cell metabolism and mitochondrial respiration. Here, we show that P. aeruginosa BMVs (i) reprogram cell metabolism of human lung cells, (ii) negatively affect mitochondrial respiration by (iii) specifically inhibiting complex III of the electron transport chain, leading to (iv) the activation of adenosine monophosphate-activated protein kinase (AMPK) signaling, which in turn results in (v) AMPK-dependent inhibition of global protein synthesis.