In many infections, bacteria and fungi form sticky biofilms. These comprise individual microbes stuck together in a self-produced slimy matrix. Biofilm infections are often found in people whose normal defences against infection are compromised (such as non-healing infected ulcers in people with diabetes, or lung infections in people with the genetic condition cystic fibrosis), or who have a an indwelling medical device (like an endotracheal tube to connect them to a hospital ventilator). Our research focusses on opportunistic bacterial pathogens like Pseudomonas aeruginosa, Staphylococcus aureus and other members of the ESKAPE group of priority pathogens. These species are major causes of biofilm disease.
We build and use high-validity models of biofilm infection to understand why bacteria can form long-lived, antibiotic-resistant infections in different host sites. We look at how bacteria change their biofilm architecture, gene expression, metabolism, virulence and antibiotic susceptibility when they grow in models that mimic the lungs of people with cystic fibrosis, an endotracheal tube inside a patient, or a wound. We also use these models to test the activity of new antibacterial agents. These include natural products derived from historical infection remedies, which we reconstruct in our lab through collaboration with colleagues from the arts & humanities. We also work with partners who are developing antimicrobial polymers, small molecules or bacteriophage.
OUR MODEL OF BIOFILM IN CYSTIC FIBROSIS LUNG
We developed a novel ex vivo system to study how Pseudomonas aeruginosa and other bacteria interact, evolve and become resistant to antibiotic treatment during chronic lung infection. As explained in the video below, we use pig lungs from a commercial butcher and culture them in the lab in conditions that closely mimic chronic cystic fibrosis infection. This lets us study pathogen pathology, community ecology and evolution in a very realistic context. Because the lungs we use are a waste product from pigs slaughtered for meat, this model is also very ethical and, in the future, its wider adoption could reduce the use of live animals in infection research.
Our research using the lung model has been funded by the Medical Research Council, the Biotechnology & Biological Sciences Research Council, and the National Biofilms Innovation Centre.
ANCIENTBIOTICS: CAN WE FIND NEW ANTIBIOTICS BY LEARNING FROM HISTORY?
Throughout history, people have suffered from infectious diseases. From the Black Death to modern “superbugs” like MRSA, troublesome microbes have caused illness, death, and changes in our behaviour and society. Our lab is part of a team of researchers from different disciplines – microbiologists, philologists, medicinal chemists and pharmacologists – who are working together to study the history of infectious disease, and to see if it can inform our future responses to pathogens. You can read more about the interdisciplinary team and our projects here.
Medieval European manuscripts contain numerous remedies for microbial infections, and the Ancientbiotics team has conducted detailed research into a reconstruction of an early medieval Englishremedy for eye infection. The remedy is highly bactericidal against biofilms of Staphylococcus aureus and othera common causes of antibiotic-resistant soft tissue infections. Importantly, the recipe’s efficacy relies on combining several ingredients, rather than one single active compound.
Our work has thus far led to a Phase I safety trial of this preparation, and we are working to develop a synthetic version of this natural product cocktail amenable to development into an antimicrobial wound dressing. This work has most recently been funded by Diabetes UK and the MRC.