Article
David Livermore Norwich Research Park

'One bug, one drug’ tool offers new antibiotic hope

By Rachel Holdsworth - 10 February 2014

A diagnostic test that can rapidly pinpoint bad infection-causing bacteria is being pioneered on the Norwich Research Park to assist in the advancement of a ‘one bug, one drug’ approach to antibiotic development.

The new screening approach will pave the way for specific antibiotics to be designed, creating a market for new treatments and advancing the race to overcome antibiotic resistance.

The new test should allow bacteria to be identified directly from blood samples, accelerating diagnosis and enabling the most appropriate antibiotic to be administered within hours.

The collaborative project is led by the University of East Anglia (UEA). Professor David Livermore, an expert in medical microbiology from the MedicalSchool at UEA, explains that overuse of broad-spectrum antibiotics drives the spread of resistance.

He says: “A patient with a severe infection has the highest chance of a swift recovery if they receive effective antibiotics without delay. However, the doctor doesn’t know what bacteria are causing the infection until the lab results arrive two days later, so current clinical practice is to prescribe a broad-spectrum antibiotic that should destroy all of the likely bacteria.

“Unfortunately, these powerful drugs also destroy many other “good” bacteria in the body. This can lead to the gut being colonised with Clostridium difficile, causing diarrhoea and disease.

“What’s more, these broad-spectrum antibiotics exert a Darwinian process of natural selection on gut bacteria, favouring those that are resistant and resulting in the emergence of ‘superbugs’.  Some of these may later cause infections, for example if they reach the urinary tract.

“Finally, new broad-spectrum antibiotics tend to be based on existing drugs and already have pockets of resistance before they are even released.”

The Norwich Research Park hosts one of the largest groups of microbiologists in the world and this multi-disciplinary expertise is creating the knowledge-base essential for a new approach to antibiotic development and the treatment of infections.

Advances in molecular biology mean it will be possible to identify the bacteria within hours using a blood sample taken from a patient with an infection rather than days using traditional culture methods.

This improved diagnosis is being made possible by the development of next-generation sequencing technology, a speciality of The Genome Analysis Centre (TGAC) also situated on the Norwich Research Park.

Professor Wain, professor of medical microbiology at UEA, is working closely with colleagues at the Norfolk and NorwichUniversityHospital and TGAC to trial diagnostic methods based on next generation sequencing technology.

He says: “NHS microbiology has largely been unchanged for the last 40 years. Samples, such as urine or pus, are streaked onto agar plates so that bacteria can grow overnight.  The bacteria in these cultures are then identified and tested with antibiotics to see which they are sensitive to, which takes a further 24 hours.  

“Next-generation sequencing is like a molecular version of the agar plate – only better. We may even be able to say if the organism is resistant to antibiotics.

“The development of rapid diagnosis will make it easier to develop new drugs that are specific to a particular pathogen. This means that narrow-spectrum drugs that cure the infection and do least harm to the body’s normal flora can be used instead of broad-spectrum drugs. It is this technology that is paving the way for the development of new antibiotics that target only ‘bad’ bacteria.”

Professor Wain and his colleague Dr David Williams have set up Discuva, a drug discovery company focused on finding new, more narrow-spectrum antibiotics.

The company has developed a high-throughput screening engine that is able to find new classes of antibiotics for new molecular targets.

Dr Williams says: “Unlike broad-spectrum antibiotics, the molecular targets for narrow-spectrum drugs only need to exist in a limited number of bacterial species, so this increases significantly the possibilities of finding new classes of antibiotic.

“With our platform technology it is possible to identify a novel antibiotic target for any bacteria and also ascertain potential mechanisms of resistance. This means that we are able to provide a comprehensive prediction of how our antibiotics will behave in human clinical trials and whether they will go on to produce safe effective medicines.”

A high-throughput screening technology for new, narrow-spectrum antibiotics and the simultaneous development of fast diagnostics therefore has the potential to overcome the burden faced by pharma companies of proving safety and efficacy and it could potentially open a new era of antibiotic development.

Regulatory complexity has slowed down the introduction of new antibiotics. Between 1950 and 1960, eight classes of antibiotic were introduced for human use - but in the last 40 years there have been just five.  Coupled with the rising threat of antibiotic resistance, this leads many to believe that we are fast approaching a ‘post-antibiotic era’, where common infections can no longer be treated and may even prove fatal.

Discuva’s technology has the potential to reverse this trend. 

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