Biofilm-REsponsive Adjuvant as novel THerapeutic approach

The aim of the Biofilm-REsponsive Adjuvant as novel THerapeutic approach (BREATH) project is to help people affected by mucoviscidosis by improving the treatment of lung infection. Mucoviscidosis (also called cystic fibrosis, CF) is a rare disease originating from a genetic mutation, which affects 1 child in every 2000 births, corresponding to around 40 000 people in Europe. Patients with CF- disease will suffer from impaired respiratory function with recurrent lung infection. Cystic fibrosis can still not be cured and the life of patients is shortened due to the accumulated damage of their lung associated with poor respiratory function. Because of the presence of a sticky mucous secreted in the lung of CF-patients, bacteria (with Pseudomonas aeruginosa being predominant) will develop rapidly and form a biofilm. The specificity of this biofilm relies in this composition, with high amount of alginate. Alginate is a polysaccharide that obstructs the airway of CF-patient and protects the microorganisms from therapies. To prevent further spreading of infection, medical treatment includes prolonged course of antibiotics, given orally, intravenously or by inhalation. Unfortunately, those antibiotic regimens must be repeated, as bacteria embedded in an alginate-rich biofilm are impossible to eradicate. As very few antibiotics have been discovered since several decades, the scientific community must focus its effort in optimising the efficacy of the ones currently available, which is the goal of the BREATH project. The final aim of BREATH project is to screen and identify small molecules, administrated as adjuvant to antibiotics, that will enhance the efficacy of the drugs and improve treatment of CF-lung infection. A key point of the BREATH project is to develop in vitro a simplified 3D model of biofilm with features and characteristics relevant to mimic CF-lung condition. This model will be produced using 3D Bioprinting, based on alginate and other import extracellular polymeric substances (EPS). At a later stage, we will then incorporate the microorganisms into this model and use it as an in vitro tool to rapidly test antibiotics and to select new adjuvants. The selected adjuvants must interact with alginate/EPS and increase its permeability to the penetration of antibiotics. To reach the goal of BREATH, this multidisciplinary project gathers scientific expertise in biomaterials, chemistry, microbiology, biointerface and pharmaceutical sciences, from TU Wien (Dr. Guillaume O and Prof. Ovsianikov A., Institute of Materials Science and Technology, 3D Printing and Biofabrication Group) in collaboration with the BOKU (Prof. Reimhult E., the Institute for Biologically Inspired Materials). If successful, our strategy could be employed to treat not only CF-lung infection but also to develop novel drug delivery systems that could potentially optimize the treatment of other biofilm and chronic infections.