The Role of Catecholamine Stress Hormones and Inotropes in the Promotion of Bacterial Growth, Virulence and Biofilm Formation

Bacteria in most environments exist and grow in association with surfaces, leading to formation of biofilms. In the medical context, biofilms are particularly significant for human health because of their high resistance to antimicrobial and immune system attack. In the health care setting biofilms associated with indwelling devices such as intravenous catheters and endotracheal tubes is a major clinical problem. It has been shown in previous reports that catecholamine stress hormones such as epinephrine, norepinephrine and structurally similar inotrope drugs used to treat heart and kidney problems in seriously-ill patients, are able to promote growth and virulence of certain bacteria. In this thesis, the role of catecholamine inotropes and stress hormones as an environmental factor for the induction of biofilm formation by infectious bacteria relevant to medical devices is considered. In vitro phenotypic characterisation was investigated by mainly using microbiological techniques, microscopy and proteomic analysis. The first section of this thesis shows how clinically attainable levels of catecholamine inotropes stimulated Pseudomonas aeruginosa growth and biofilm formation. The mechanism by which growth stimulation occurs was found to be via delivery of iron from the serum Fe-binding transferrin. P. aeruginosa growth, biofilm formation and motility were all significantly enhanced by catecholamine inotropes (P<0.05). Inotropes may be a risk factor for ventilator associated pneumonia as they stimulated biofilm formation on endotracheal tubing. In the second section which focuses on Escherichia coli and Salmonella Typhimurium, it was found that catecholamine stress hormone effect on growth, motility and biofilm formation was independent of the putative QseC and QseE catecholamine sensing receptors. In the third section, factors related to catecholamines inotropes Staphylococcus epidermidis biofilm stimulation were considered. Collectively, these findings show that levels of catecholamine inotropes found within critically ill patients can promote bacterial biofilm formation, and so contribute to bacterial pathogenesis within the hospital setting.