November 07, 2012 -- A new rapid diagnostic test for bacterial infection is being pioneered on the Norwich Research Park that will facilitate the advance of a ‘one bug, one drug’ approach to antibiotic development. The new screening approach will enable highly specific antibiotics to be designed, accelerating the race to overcome resistance and creating a market for new treatments.
It is hoped the new test will allow bacteria to be identified directly from blood samples, speeding up 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 Norwich Medical School at UEA, explains that overuse of broad-spectrum antibiotics drives the spread of resistance.
“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 is 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 University of East Anglia, is working closely with colleagues at the Norfolk and Norwich University Hospital 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, urine or pus for example, 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.
Professor Wain continues: “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, 8 classes of antibiotic were introduced for human use, 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 technology has the potential to reverse this trend.
1. Tängdén T, Cars O, Melhus A, Löwdin E. Foreign travel is a major risk factor for colonization with Escherichia coli producing CTX-M-type extended-spectrum beta-lactamases: a prospective study with Swedish volunteers. Antimicrob Agents Chemother. 2010; 54:3564-8
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About Norwich Research Park www.norwichresearchpark.com
The Norwich Research Park is a partnership between University of East Anglia, the Norfolk and Norwich University Hospital, four independent world-renowned research institutes namely the John Innes Centre, Institute of Food Research and The Genome Analysis Centre (all strategically funded by the Biotechnology and Biological Sciences Research Council (BBSRC)) and The Sainsbury Laboratory linked to the Gatsby Charitable Foundation. The BBSRC is itself a partner as is the John Innes Foundation.
The vision of the Norwich Research Park partners and local government stakeholders is to develop a thriving science and innovation business park over the next decade by supporting spin-out and start up companies and through attracting inward investment from large corporate organisations involved in science and technology. The Norwich Research Park is home to around 30 science and IT based businesses.
With over 11,000 people including 2,700 scientists, the Norwich Research Park has one of Europe’s largest single-site concentrations of research in Health, Food and Environmental Sciences.
In 2011, the Government awarded BBSRC £26M to invest in Norwich Research Park to deliver innovation from the research base and generate economic growth and job creation. The investment will help to create and support new companies and jobs based on world-leading bioscience.
About the University of East Anglia
The University of East Anglia (UEA) is ranked in the top one per cent of universities in the world and is consistently in the top ten for student satisfaction. It is a leading member of the Norwich Research Park, one of Europe’s biggest concentrations of researchers in the fields of environment, health and plant science. www.uea.ac.uk.
UEA’s Norwich Medical School has a reputation for exciting and innovative approaches to education, supported by a strong and rapidly developing research programme. Around 90 per cent of UEA research was rated internationally excellent in the last Research Assessment Exercise, with over 50 per cent ‘world leading’. www.uea.ac.uk/med
About The Genome Analysis Centre (TGAC) www.tgac.ac.uk/
The Genome Analysis Centre is a specialist in genomics and bioinformatics, with focus on interpretation of data to enable and drive the use of bioscience in research and industry.
The Genome Analysis Centre is one of eight institutes that receive strategic funding from the BBSRC.
About Discuva Ltd www.discuva.com/
Discuva is a drug discovery company focused on the creation of Next Generation targeted antimicrobials against new emerging and drug-resistant bacterial pathogens.
Antimicrobial drugs in the 21st century – 25th September 2012
Co-ordinated by Professor Wain of University of East Anglia and Dr David Williams of Discuva Ltd, this one-day conference bringing together approximately 200 delegates from academia, industry, healthcare services and funding groups to discuss practical solutions for treating human bacterial diseases.
This meeting plans to explore recent advancements in diagnostics, highlight novel treatments and outline new anti-microbial healthcare paradigms to address the emerging threat of drug-resistant pathogens.
More information can be found at http://www.discuva.com/One_Bug_Flyer.pdf