In vivo evaluation of biofilm-related pneumonia.

Biofilm formation during lung infection is related to persistent infection. This is a characteristic of chronic diseases such as Cystic Fibrosis (CF). Moreover, biofilm formation in endotracheal tubes (ETT) is related to the onset of Ventilator-Associated Pneumonia (VAP). Failure in treatment is associated with high morbidity and mortality. In addition to increased resistance, antibiotic therapy failure can also result from regrowth of a subset of cells in bacterial populations that are called persisters. When challenged with a lethal dose of antibiotics, this small fraction of transiently antibiotic tolerant cells survives to give origin to a new population and they are then related to the chronic nature of pneumonia. Therefore, new ideas to prevent and treat biofilm-related lung infections are required. New antibacterial targets and incorporation of antibacterial compounds in 3D printed catheters are being investigated. A chronic P. aeruginosa lung infection model, based on intratracheal infection of bacteria encapsulated in seaweed alginate beads, was optimized to characterize persistence in collaboration with KULeuven. This animal model mimics cystic fibrosis (CF) and several low and high persister laboratory strains are currently being studied in vivo to validate the infection dose and the treatment scheme for persistence studies. Natural isolates from other clinical settings, including animal and environmental origin, will also be tested. The VAP model is in the framework of an H2020 ETN project called PRINT-AID. The aim of this project is to proof the value of developing a new generation of 3D-printed personalized medical devices with antimicrobial functionalities. Screening of new drug leads, in vitro testing in dynamic biofilm systems and cell models and improvement of the manufacturing process of 3D printed and coated catheters are currently being performed by collaborators. UAntwerp will be responsible for the development of a VAP mouse model in which the 3D produced tubes will be inserted in the main bronchus intratracheally. The tubes will be inoculated with biofilm-forming S. aureus and with this model we aim to evaluate the inhibition of bacterial adherence to the tubes in vivo and the anti-infective efficacy of the tubes by assessing the bacterial burden in the lungs.

Keywords:BACTERIOLOGY

Disciplines:Bacteriology