BubblEs for TArgeting and TReatment of biOfilm InfectioNs (BETATRON)

Lead Research Organisation: University of Leeds
Department Name: Physics and Astronomy


Antimicrobials, commonly known as antibiotics, are becoming less effective because of resistance. Antibiotic resistance is when bacteria or other microbes change so that antibiotics no longer work to treat infections. Antibiotic resistance is a global problem that is being made worse by antibiotic overuse. We can combat antibiotic resistance by developing better antibiotics as well as improving the way we use existing ones. Patients will continue to need antibiotics, particularly to treat serious infections, like sepsis, so we need to improve how they are used. Right now, 'broad-spectrum' antibiotics, that kill a wide range of bacteria, are often given in high doses to ensure that enough antibiotic reaches the microbes at the site of infection. Much higher doses than would be needed if we could deliver antibiotics just at the site of infection are used. These antibiotics kill many of the beneficial 'resident' bacteria living in our bodies, which drives resistance. It would be much better if we could use a 'personalised medicine' approach where antibiotics are delivered locally, at the site of infection, at doses necessary to treat the problem. By giving lower doses of targeted treatment and avoiding exposure of the normal colonising bacteria to antibiotics, our vision is to improve health outcomes and reduce the selection of resistant microbes.

Our project involves using tiny bubbles similar to those already used with ultrasound scanning to study the flow of blood through the heart and are currently being tested to treat cancers. These bubbles are given by injection into a vein. We propose to develop bubbles so that they can deliver antibiotics directly to a site of infection. The bubbles can also be burst using higher powered ultrasound, which is another possible way to kill bacteria. The bubbles are tiny, not much bigger than the bacteria, and will be coated with molecules that will allow the bubbles to stick to the surface of specific bacteria. This is known as 'molecular targeting'. By combining bubbles with ultrasound to trigger the release of antibiotics just at the site of infection, we aim to reduce the amount of antibiotics required to kill bacteria, without killing the helpful bacteria that live elsewhere in the body. Antibiotics often fail because the bacteria create their own local environment, the "biofilm", full of sticky chemicals, which also reduces the killing effects of antibiotics. Our approach will harness the energy released when an ultrasound pulse bursts bubbles to help drive drugs deep into this "biofilm" and hence help kill bacteria more effectively. In addition to getting more antibiotic into a biofilm, these drug-loaded bubbles will allow us to deliver new types of drugs, e.g. antimicrobial peptides (AMPs). AMPs are very effective at killing bacteria, but many cannot be given in the usual way, via a drip, into a vein to treat infections because they tend to be broken down in the blood before getting to the infection site. We can overcome this problem by loading the AMPs into tiny protective capsules attached to the bubbles and release them where/when they are required. Finally, we plan to investigate if bacteria can be released from their local biofilm environment using bubbles plus ultrasound. Here we will harness the mechanical energy released by bursting bubbles to break up the biofilm. The bacteria released from the biofilm are known as 'planktonic' and are more susceptible to conventional antibiotic treatments.
In summary, we propose to:
1. Develop new targeting agents to bind bubbles to bacteria and new drug-loaded cargoes to kill bacteria/ destroy biofilms.
2. See if bubbles and ultrasound can be used together to deliver drugs into bacterial biofilms and kill bacteria more effectively.
3. Use our approaches to deliver drugs that cannot currently be used to treat patients because they are broken down in the blood.


10 25 50

Description Kimal 
Organisation Kimal
Country Germany 
Sector Private 
PI Contribution Developing microbubble approaches for the prevention/ removal of infections in catheters
Collaborator Contribution Kimal - provide catheters of different materials and dimensions - and will provide expertise around current methodologies to reduce /prevent infections
Impact Early stage as - not outcomes
Start Year 2022
Description Malvern Panalytical 
Organisation Malvern Panalytical
Country United Kingdom 
Sector Private 
PI Contribution We are developing new ways to use their equipment and to test measurement for buoyant particles
Collaborator Contribution They provided and instrument - estimated cost to buy would be £80000
Impact one paper by Batchelder etal so far
Start Year 2022
Description Evening event - Quantum Sauce 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Evening science event - 3 speakers on varied topics plus quiz
Year(s) Of Engagement Activity 2022
URL https://theconstitutional.co.uk/event/4738414/605482145/quantum-sauce-fri-2-dec
Description Invited Keynote 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Nanobubbles 2022 - international Conference
Year(s) Of Engagement Activity 2022
URL https://www.nanobubble2022.ovgu.de/