Tackling antibiotic resistance

Antibiotics have been a leading factor in combating disease and extending life expectancy for the last 100 years. Diseases such as pneumonia, sepsis, neonatal meningitis and urinary tract infection are now easily treated and wound infections from surgery and dentistry can be prevented.

Many strains of bacteria, however, have become resistant to drugs discovered during the ‘golden age’ of antibiotic drug development in the 1950s and 1960s, posing a significant threat to current and future health. The World Health Organisation warns that without effective antibiotics, the success of major surgery and cancer chemotherapy would be extremely compromised.

Big pharmaceutical companies are no longer investing in the development of low-profit antibiotics, however, and the pipeline for new antibiotics is running dry. But as part of an innovative global network of academic and industry partners, the University of Oxford is identifying ‘inhibitors’ for use in combination with the β-lactam class of antibiotics to tackle antibiotic resistance.

β-Lactams represent 60% of total antibiotic sales and are among the safest and most effective antibiotics. The Oxford project, which originated from work performed in Professor Chris Schofield’s lab, has identified a new class of inhibitors which, if administered along with the carbapenem group of β-lactams (used as a last-resort drug in hospitals), will suppress resistance even in the most virulent superbugs. The project is expected to start human trials in 2021/2.

The project is supported by the European Innovative Medicines Initiative funded ENABLE (European Gram-Negative Antibacterial Engine) programme, which includes universities, pharmaceutical companies and contract research organisations in Europe, the United States, and elsewhere.

Project Leader, Jürgen Brem, explains the importance of the collaboration. “Getting a new drug or therapy from ‘bench to clinic’ is normally a slow process. The ENABLE network is a collaboration of extremely committed and experienced people, with a real passion for antibiotic research. Being able to draw on the network, and the rapid development of new knowledge by partners with specialist expertise, have been crucial in getting the new drug candidate to this stage.”

A key goal of the project will be creating a therapy which will also be useful to developing countries. “Producing something for countries in the Global South is part of our vision,” explains Brem. “Places such as India, Pakistan, Brazil and China are particularly affected by antibiotic resistance but cannot afford expensive new drugs. Making a drug that is losing its effectiveness work again makes a lot of sense in this context.”

“The ENABLE project is a rare successful example of an advanced drug discovery programme embedded within a university,” continues Brem. “It’s really exciting to be part of this and continue Oxford’s longstanding success in antibiotic research. Sir Howard Florey tested and developed penicillin for first patient use in Oxford in 1941; and Dorothy Hodgkin used X-ray data to identify the molecular structure of penicillin here in 1945. We are proud that our work tackling antibiotic resistance continues this important legacy.”

Dr Jürgen Brem is a Junior Research Fellow St Cross College and a Postdoctoral Research Assistant at Department of Chemistry, Chris Schofield lab.

Funders: ENABLE (European Gram-Negative Antibacterial Engine), a programme of the European Innovative Medicines Initiative