Advancing phage therapy for the treatment of Burkholderia cepacia complex infections in people with cystic fibrosis

Infections caused by the Burkholderia cepacia complex (BCC) group of bacteria cause dangerous lung infections for people with CF and they’re very difficult to treat. In this Early Career Researcher Development Award, University of Leicester-based Dr Jessica Lewis is advancing research into an alternative treatment to antibiotics known as phage therapy. 

Summary of study

Infections caused by the Burkholderia cepacia complex (BCC) group of bacteria cause dangerous lung infections for people with CF. The infections are particularly difficult to treat with antibiotics due to antimicrobial resistance. 

Bacteriophages or ‘phages’ are viruses that can kill bacteria and may be an effective way to treat lung infections in people with CF as an alternative to antibiotics or alongside them. Early career researcher Dr Jessica Lewis, based at the University of Leicester, has been awarded Development Award funding to further explore exciting preliminary results from lab-based studies investigating new phage treatments for BCC. 

I hope that my research will optimise phage treatments for BCC lung infections in people with CF and provide a more streamlined and faster access to phage treatments for those who really need them. On a personal note, it gives me the opportunity to do research in the memory of a friend I lost to CF.

Dr Jessica Lewis.

Read about the research studies in more detail below

  • Increasing the ‘bank’ of phages to create a phage therapy

    Dr Lewis will look for new phages that act against BCC to increase the chances of a successful phage therapy in the future. Phages can be found in unusual places, such as waste water and sewage. Lots of different phages will be removed from these samples and tested in the lab. They will be analysed for anything that would make them unsuitable for a phage treatment, such as toxins or antimicrobial resistance genes, and they’ll also be tested to see if they can effectively kill Burkholderia cepacia complex infections. Next, they’ll be tested to check they could work as a medicine, such as the necessary storage conditions and the pH (acid-alkali balance) required to administer the new medicine. Alongside looking for phages from environmental sources, Dr Lewis will also create new phages using genetic modification of existing phages.

  • Testing phages in lab models of the lungs

    The next step of testing phages is to test them in the lab, in a way that mimics what’s happening in the lungs. The newly found phages from the first work package will be tested alongside two existing phages effective against BCC that Dr Lewis has found and studied previously. 

    When bacteria such as Burkholderia cepacia complex grow in the lungs of people with CF, they adapt and change. This includes developing defences against antibiotics and other forms of treatment. In addition, BCC bacteria grow alongside many other species of bacteria, fungi and viruses within the lungs. All these bugs interact with each other, and change the way that a specific bug will respond to treatment. 

    Studies using a lab models will provide more information on how and whether these phages are able to overcome the defences of the bacteria, and their effectiveness as a potential treatment in the presence of other bugs.

  • Learning how to produce large quantities of phage for therapy

    Huge numbers of phages are needed to have enough to deliver an effective phage therapy (It can be as many as a trillion – 1,000,000,000,000). 

    When a single phage infects a single bacteria, it uses the bacteria to produce hundreds more phages, that eventually cause the bacteria to burst open (killing the bacteria) and releasing new, identical phages to attack other bacterial cells nearby.

    The production of phages for a phage therapy, takes advantage of this natural ‘phage-making’ process. However, the bacteria used for the phages to infect needs to be carefully studied and adapted to make enough of phages for a future medicine and ensure its safe, and effective as possible.

    In the third work package of her Development Award programme Dr Lewis will study and adapt a lab strain of Burkholderia cencepacia to create a ‘phage production strain’ of bacteria.

Who’s involved?

Principal investigator: Dr Jessica Lewis, University of Leicester

Co-investigators:

Professor Eshwar Mahenthiralingam, Cardiff University
Dr Andrew Millard, University of Leicester
Dr Freya Harrison, University of Warwick
Professor Jo Fothergill, University of Liverpool