Effect Of Catecholamines And Inhaled Drugs On The Growth And Virulence Of Bacterial Respiratory Pathogens

Background: Pseudomonas aeruginosa (P. aeruginosa) and Burkholderia cenocepacia (B. cenocepacia), a member of the Burkholderia cepacia complex (Bcc) are common biofilm forming pathogens in Cystic Fibrosis (CF) patients. Bcc contributes to mortality in CF lung transplantees. Drugs such as catecholamines and salbutamol are known to interact with bacteria in general. In CF and post transplanted patients, both these drugs are commonly used and can possibly interact with P. aeruginosa and B. cenocepacia, and enhance their virulence. Aim: 1. To evaluate whether catecholamines affect the growth and virulence of B, cenocepacia. 2. To evaluate whether Salbutamol affects the growth and virulence of B. cenocepacia and P. aeruginosa. 3. To evaluate whether there was any interaction of Burkholderia with the ciliary epithelium and if the drugs catecholmaines and salbutamol affected this. Methods: In vitro methods for growth, attachment and biofilm formation were carried out for B. cenocepacia with drugs, catecholamine and salbutamol, and for P. aeruginosa with salbutamol. To give a clinical context, biofilm formation on endotracheal tubes and ex vivo studies on healthy and CF airway epithelial cultures with and without supplemental drugs were carried out. Results: B. cenocepacia were found to be catecholamine responsive organisms. Catecholamines increased the growth and biofilm formation of B. cenocepacia. Salbutamol did not influence the growth of either B. cenocepacia or P. aeruginosa, but increased the cell to cell aggregation. On endotracheal tubes both drugs enhance the formation of mature biofilms. B. cenocepacia infection on airway cultures did not affect ciliary beat frequency but attached to ciliary tips by five hours and was able to form mature biofilms and this was enhanced in presence of catecholamines and in CF epithelial cultures. Summary: Catecholamines increase the growth, attachment and biofilm forming ability of B. cenocepacia. Salbutamol, a commonly used respiratory drug has an influence on the cell to cell aggregation for bacteria. B. cenocepacia produce biofilm within 5 hours after infection of the airway epithelium especially in CF epithelial cultures and more so with catecholamines. This observation is relevant to CF patients to guide clinical practice and detect mechanism of bacterial infection which may offer a therapeutic target for CF patients.