Developing better treatments for lung infections caused by Mycobacterium abscessus

Mycobacterium abscessus infections are very difficult infection to treat and the antibiotics used have very severe side effects. In this Strategic Research Centre (SRC) award, University of Cambridge-based Professor Andres Floto and colleagues will explore better ways to use existing antibiotics and explore innovative new ways to treat these infections.

Summary of research proposal

Mycobacterium abscessus (M. abscessus) is a bacteria that causes lung infections in people with CF. M. abscessus is one of the ‘non-tuberculous mycobacteria’ (NTM) group of bacteria. It is a very difficult infection to treat and the antibiotics used have very severe side effects. For example, treatments involve a combination of antibiotics usually taken for between one or two years and fail clear the infection in many people. There are currently no licensed medicines that specifically treat M. abscessus infection. 

There is therefore an urgent need to develop more effective treatments for M. abscessus infections. Research studies within this Strategic Research Centre will address this in three ways: 1) to discover better ways to use existing antibiotics, 2) to adapt existing antibiotics to improve their effectiveness and reduce their toxicity and 3) to develop and refine innovative new ways of designing new antibiotics from scratch .

These advances will improve chances of treatment success for M. abscessus infections, reduce the risk of antibiotic resistance developing, and will reduce side effects, complications, and treatment burden for people with CF. 

Research studies in more detail

  • Discovering better ways to use existing antibiotics

    Treatments for M. abcessus infections require people to take a combination of antibiotics at once. The strategy of taking multiple antibiotics at once is also used to treat related infections such as tuberculosis (TB). (TB is caused by the bacteria Mycobacterium tuberculosis). New combinations of antibiotics to treat TB are currently being tested in clinical trials.

    Researchers working in this project within the SRC will investigate whether antibiotics showing promising results as treatments for TB might also work for M. abscessus infections. A set of antibiotics will be tested step by step to assess their effectiveness as combination treatments. These studies could lead to new combinations of antibiotics being tested in the clinic within a few years.

  • Adapting existing antibiotics

    The aim of this project is to use innovative chemical techniques to improve existing antibiotics, increasing their effectiveness and reducing their toxicity. Old antibiotics no longer used due to their toxicity could become a treatment option again.

    The researchers plan to develop ways to keep the antibiotics inactive until they reach M. abscessus. They plan to do this in two ways, one is to design medicines that only become active in the presence of bacteria. This works as the bacteria produce an enzyme that converts the antibiotic into the active form. The second approach is to add a ‘targeting’ protein to the antibiotics, so they only become active when the target locks onto the bacteria.

    These new versions of old drugs should move more quickly through the drug development process, meaning they could become a treatment more quickly than designing a completely new medicine. 

  • Refining a new way of designing antibiotics

    Bacteria have a number of ways to protect themselves against antibiotics. These include preventing the antibiotic from entering the bacteria, quickly removing the antibiotic if it does get inside or by chemically inactivating antibiotics inside the bacteria. Researchers within the SRC have already worked out some ‘rules’ that mean chemicals avoid these defences and stay inside bacteria. 

    Future medicines that follow these chemical rules may be extremely effective antibiotics. The aim of this project within the SRC is to use the rules to design chemicals that could become new antibiotics and quickly test their effectiveness. Some of their testing will use AI and computer-led (‘in silico’) drug design.

    If successful this work could impact how antibiotics are designed by drug companies and should make it easier to design antibiotics for any infection-causing bacteria in the future.

Who's involved?

Principal investigator: Professor Andres Floto, University of Cambridge

Co-investigators:

Professor David Spring, University of Cambridge

Professor Jose Miguel Hernandez Lobato, University of Cambridge

Dr Iris Batalha, Institute of Bioengineering of Catalonia, Barcelona

Dr Vitor Mendez, University of Cambridge