Corticosteroids impact P. aeruginosa biology. Corticosteroids modulate biofilm formation and other virulence-related features of Pseudomonas aeruginosa

Corticosteroids are anti-inflammatory drugs commonly administered to patients with chronic obstructive pulmonary disease (COPD), in which persistent infection by Pseudomonas aeruginosa is frequent. Recent works questioned the corticosteroids’ therapeutic value in COPD, even proposing them as a risk factor for infection. This was linked to undesired effects in the host’s immunity possibly due to the impact of the drug on bacterial biology. The objective of our work was to ascertain this possibility, and in this regard we show that corticosteroids commonly used in COPD by inhalation route (budesonide and fluticasone propionate) significantly attenuate the P. aeruginosa intrinsic inflammatory properties and cause a decrease in its cytotoxicity and cellular invasiveness figures. Our results reveal that corticosteroids boost P. aeruginosa biofilm formation in a time- and dose-accumulative fashion, as well as the release of outer membrane vesicles and extracellular DNA (key component of the biofilm matrix). We also show that the accumulation of the signalling molecule c-di-GMP, responsible for the switch from planktonic to biofilm mode of life, increases in response to corticosteroids, which could in turn explain the abovementioned phenotypes. Future work will determine the exact underlying mechanisms of these findings and their in vivo implications, but our data suggest that corticosteroids may mediate a fast acquisition of advantageous features classically related with P. aeruginosa long-term adaptation to the chronic lung niche, thus facilitating of the chronic persistence of this kind of infections.