Analyzing the effects of benzodiazepines on the virulence and biofilm formation of Pseudomonas aeruginosa.

Sedation with benzodiazepines (BZs) has eventual side-effects increasing the risk for ventilator-associated pneumonia (VAP) (e.g. immunity alterations and nervous/mechanical responses), but there are some knowledge gaps on the topic. For instance, whether BZs could cause a modulation of bacterial virulence, and/or influence the host-pathogen interaction in neglected contexts to facilitate VAP. Consequently, we analyzed relevant in vitro and in vivo infection-related parameters to decipher whether they could be affected by BZs to increase the success for infection of the top VAP-causing pathogen Pseudomonas aeruginosa. While most variables were unaltered, an attenuated pathogenic impact on lung A549 cells (invasion, cytotoxicity and inflammation reduced up to ≈ 50%) appeared upon BZs exposure at high therapeutic concentrations, potentially because of effects mostly on the cultured cells. These facts could entail a BZs-associated stealth pathogen-like behavior of P. aeruginosa consisting of a weak immune activation proportional to the mild damage caused, perhaps favoring VAP onset. BZs also triggered a significantly increased biofilm formation (up to ≈ 2-fold > controls) on plastic plates and endotracheal tubes (supported by the upregulation of biofilm-related genes/KEGG pathways and increased c-di-GMP accumulation), suggesting the BZ-dependent boosted formation of these sessile reservoirs which could potentially increase bacterial release to low airways and thus VAP progression.