New paradigms for antibiotic discovery and production

Currently, it is estimated that around 700,000 deaths worldwide result from antimicrobial resistance each year. Unless action is taken, this is projected to rise to 10 million deaths each year by 2050, with the added impact of a cumulative $100 trillion of economic output at risk due to the rise of drug-resistant infections.

Antibiotics underpin modern medicine as we know it: if they lose their effectiveness, key medical procedures (such as caesarean sections, joint replacements, and treatments that depress the immune system, such as chemotherapy for cancer) could become too dangerous to perform.

700,000 deaths worldwide result from antimicrobial resistance each year

There are various recommendations on how to tackle this problem, including enhancing public awareness and promoting new, rapid diagnostics in order to cut unnecessary or inappropriate use of antibiotics. One solution on which NPL is working is to increase the number of effective antimicrobial drugs to defeat infections that have become resistant to existing medicines.

In response to the challenge, NPL is working to discover, screen and validate new classes of antimicrobials that exhibit effective mechanisms against pathogens. Combining this world-class measurement expertise with Ingenza’s experience as the UK’s premier industrial biotechnology company to engineer efficient and adaptable biomanufacturing systems is a natural fit.

The success of the first antibiotics, such as penicillin, was based on their ability to not only combat infection, but also be redesigned to enhance effectiveness, resulting in longevity and sustainability of useful antibiotics. NPL and Ingenza are therefore creating a new family of antibiotics, by enhancing the design and measurement of antibiotics that selectively attack microbial cells.

This August, Ingenza and NPL kicked off a three-year collaboration with Dr Mathew Upton’s group at the University of Plymouth, thanks to a grant from Innovate UK. Dr Upton’s group is internationally recognised for the discovery and development of epidermicins, a novel class of antibiotics.

The goal is to generate a pipeline of candidate molecules to deliver the most effective treatment

The epidermicin class of bacteriocins are naturally-occurring toxins produced by bacteria to kill other, closely-related strains. The specific range of bacteria that epidermicins naturally target already offers an initial clinical application to combat hospital-derived MRSA infections (commonly known as ‘super bugs’ as they are drug-resistant). However, if a systematic approach can be found to adapt these bacteriocins into more broadly effective or even more potent antibiotics, they could increasingly challenge the growing problem of antibiotic resistance and the threat this poses to human health.

This unique consortium is extremely well-placed to take forward joined-up discovery, development and manufacture in ways which have never been done before

NPL’s experimental approach will help establish the critical performance criteria for selected epidermicins, their derivatives and related bacteriocins. This should in turn enhance the range of bacteria they can kill as well as the potency at which they can do this. The goal is to generate a pipeline of candidate molecules to deliver the most effective treatment while minimising any potential side effects. Within the same project, the team will also work to optimise the efficiency and adaptability of Ingenza’s fermentation based manufacturing platform to scale up production of each promising new antimicrobial candidate for further testing and clinical trials.

This isn’t the first time NPL’s expertise has been critical in tackling this huge global health challenge – just last year they worked with UCL to convert a breast milk protein into an artificial virus that kills bacteria on contact. The collaborative nature of the project was again the winning ingredient – funded by EPSRC, BBSRC and the Department for Business, Innovation and Skills, measurements were also performed at the Diamond Light Source.

The advance of antimicrobial resistance is relentless and well-documented. There is a clear need to develop new antibiotics, but in doing so we must ensure that these new antibiotics can be adapted to keep pace with changing resistance. This unique consortium is extremely well-placed to take forward joined-up discovery, development and manufacture in ways which have never been done before.

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