Biofilm-responsive adjuvant as novel therapeutic approach
Abstract
Bacteria within a biofilm are up to 1,000-fold more resistant to antibiotics and are inherently insensitive to the host immune response. This is particularly relevant for patients affected by Cystic Fibrosis (CF), also called mucoviscidosis. CF patients have a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which is responsible for the secretion of sticky mucus in the patient's airway, rendering them more vulnerable to infection. Indeed, once Pseudomonas aeruginosa colonizes the lungs, it can acquire a mucoid phenotype, which renders infection insensitive to antibiotics. Despite intense antibiotherapies, chronic lung infection in CF patients is extremely difficult or even impossible to treat, which results in high mortality. The reasons for the extreme resistance of CF-Biofilm to drugs are not yet fully elucidated, but external stresses existing in the local environment of the lung along with the copious secretion of alginate in the biofilm have been suggested to play a crucial role in P. aeruginosa tolerance to antibiotics. We hypothesize that by better understanding and then controlling how antibiotics interact with the main extra-cellular polymeric substances (EPS), we could improve existing therapies to eradicate microorganisms in mucoid biofilm. The main aims of the 4-year-project are (1) to establish relevant in vitro model of CFbiofilm, (2) to provide unprecedented insights into antibiotics interaction with EPS components, (3) to elucidate the effect of environmentally induced changes in the EPS on P. aeruginosa, and (4) to test biofilm-responsive adjuvants restoring antibiotics efficacy.
keywords Pseudomona aeruginosa cystic fibrosis exopolysaccharides alginate bioprinting adjuvant
Publikationen
Project staff
Erik Reimhult
Univ.Prof. Dr. Erik Reimhult
erik.reimhult@boku.ac.at
Tel: +43 1 47654-80211
BOKU Project Leader
15.04.2020 - 30.04.2025
Guruprakash Subbiahdoss
Dr. Guruprakash Subbiahdoss
guruprakash.subbiahdoss@boku.ac.at
Project Staff
15.04.2020 - 30.04.2025
BOKU partners
External partners
Technical University Vienna
Olivier Guillaume
coordinator