Project Summary: Antimicrobial resistance of bacterial biofilms presents a significant threat to human health worldwide. Most bacterial assemble on surfaces to form three-dimensional clusters called biofilms causing myriads of infections on chronic wounds, medical implants or morbidity in patients with cystic fibrosis. Biofilms are notoriously difficult to eliminate with antibiotics. Generally, concentrations of antibiotics too high to be used in humans are required to kill biofilms compared to unaggregated bacterial. Significant evidence has emerged which indicates that oxygen depletion in the tissue microenvironment increases antibiotic tolerance of bacterial biofilms while their susceptibility is enhanced by stimulation of aerobic respiration through oxygen supply. Similarly, bactericidal activity of most antibiotics relies on oxygen metabolism to stimulate endogenous production of reactive oxygen species (ROS). Co-delivery of molecular oxygen and antibiotics to bacterial biofilms can attenuate antimicrobial resistance. Hyperbaric oxygen therapy (HBOT) is the conventional technology for tissue oxygenation. However, this technology is not suitable for local oxygen delivery, particularly an ischemic tissue environment. In addition, HBOT is expensive and not readily accessible.
The possibility to develop novel nanomaterials approaches able to self-generate molecular oxygen and aid sustained release of antibiotics would represent a leap forward in the development of a new technology to restore aerobic respiration in bacterial biofilms and enhance efficacy of antibiotic therapy against chronic infections such as in chronic wounds. The proposed project aims to create a novel organic-inorganic hydrogels platform with oxygen self-generating ability to improve aerobic respiration and facilitate biofilms susceptibility to antibiotic therapy. The system offers socio-economic and fundamental advantages over state-of-the-art oxygenation and antibiotic therapies that are either not affordable, readily accessible or ineffective against biofilm infections. By co-encapsulating oxygen-generating nanomaterials and antibiotics, we aim to investigate a crosstalk of oxygen delivery and antibiotics efficacy against both Gram-negative and Gram-positive bacterial, aerobic and anaerobic strains. This information will aid the design of novel biomaterials that either prevent bacterial colonization or destroy established biofilms.
Training: The project provides excellent multidisciplinary training opportunities in bacterial culture, biofilm growth, drug susceptibility testing, microscopy and image analysis, oxygen level measurements, hydrogels preparation and characterization, statistical analysis, and scientific writing, and oral presentation.