Staphylococcus aureus (S. aureus) is a bloodstream infection that has mortality rates of 17-46% and is a daily occurrence, with over 12,700 cases in England per year. It is a significant cause of hospital-acquired infection and leads to extended hospitalisation, at an estimated cost per patient of £8k pa. S. aureus forms biofilms, a complex mixture of biopolymers and bacterial cells, on internal organ surfaces, implants, and vasculature. The biofilm structure shields most bacteria from any antibiotics leading to poor efficacy in the treatment of infection whilst having adverse effects on the microbiome. This poor localised delivery coupled with the emergence of antimicrobial resistance means that new approaches are needed to continue treating such infections.
In Leeds, we have used ultrasound (US) waves to burst tiny bubbles coated with drugs, to treat tumours effectively.
1 We have also developed some novel drugs, antimicrobial peptides (AMPs), that are selective at killing bacteria whilst leaving human cells intact.
2 However, these drugs often get broken down by enzymes in the bloodstream before reaching the infection site reducing their efficacy.
In the project outlined here, we propose to protect the AMPs by hiding them in a polymeric shell surrounding the bubbles. Ultrasound will then be used to trigger the release of the drug are the site of infection by bursting the bubbles. Further, in addition to the localised delivery of drugs, we will investigate the additional benefit of physically disrupting the biofilms using US to enhance drug delivery deeper into the biofilms and for the treatment of released ‘planktonic’ bacterium.