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Virus pill may aid C diff battle

Bacteria-busting viruses have been identified which could be used to cleanse hospitals of the infectious bug Clostridium difficile.

Scientists isolated a family of bacteriophages - viruses that target bacteria - specifically geared to destroy C diff strains.

Laboratory tests show that the “phages” are effective against 90% of bugs responsible for hospital infections.

Working with American colleagues, the British researchers hope to produce virus-loaded capsules that can be swallowed by patients.

The approach offers a radical alternative to traditional antibiotics which are proving increasingly ineffective against C diff.

Lead scientist Dr Martha Clokie, from the University of Leicester, said: “Ever since the discovery of the first antibiotic, penicillin, antibiotics have been heralded as the ‘silver bullets’ of medicine. They have saved countless lives and impacted on the well-being of humanity.

“But less than a century following their discovery, the future impact of antibiotics is dwindling at a pace that no-one anticipated, with more and more bacteria out-smarting and ‘out-evolving’ these miracle drugs. This has re-energised the search for new treatments.

“One alternative to antibiotics is bacteriophages, known as phages, which unlike antibiotics, are specific in what they kill and will generally only infect one particular species, or even strain, of bacteria - referred to as the ‘host’.

“Following attachment to their hosts, they inject their DNA into the bacterium, which then replicates many times over, ultimately causing the bacterial cell to burst open. The phages released from the dead bacterium can then infect other host cells.”

The work, mainly funded by the Medical Research Council, has been conducted in conjunction with scientists from the University of Glasgow and the US company AmpliPhi Biosciences Corporation.

AmpliPhi is a pioneer in bacteriophage research and has already demonstrated the effectiveness of using viruses to treat patients with life-threatening lung infections caused by the bug Pseudomonas aeruginosa.

The current goal is to prepare a “cocktail” of C diff phages suitable for patient trials. This will involve further developing the viruses to make them effective against worldwide C diff infections and establishing production, storage and delivery systems.

Around 40 viruses that target C diff strains have been identified so far. They are the subject of patent applications by the University of Leicester.

Dr Clokie said the aim was to produce capsules containing the phages - effectively virus pills. These would be used to deliver the phages into the stomachs of patients.

She added: “C diff bacteria primarily affect our digestive system. Whilst relatively innocuous in individuals with a healthy gut flora, they pose a serious threat when our natural digestive environment is disrupted or depleted, such as after chronic antibiotic use. In such individuals, C diff infections can cause severe diarrhoea, vomiting and dehydration. Collectively, these symptoms can prove life-threatening, particularly in elderly patients.

“Two antibiotics, metronidazole and vancomycin, are routinely used to treat C diff infections in the UK, but resistance to both is rapidly increasing. What’s worse, in addition to killing the C diff bacteria, these antibiotics also destroy the ‘good’ gut bacteria, in turn increasing the potential for relapse or new infections. Consequently, C diff infections pose a substantial healthcare burden for the NHS and a significant drain on its resources.

“The key advantage of using phages over antibiotics lies in their specificity. A phage will infect and kill only a specific strain/species of bacteria. This is particularly important when treating conditions like C diff infections, where maintenance of the natural balance of gut bacteria greatly reduces the chance of relapse.”

Phil Young, chief executive and president of AmpliPhi, said “We are very excited about this partnership with Dr Clokie and the University of Leicester. Phage-based therapy has the potential to revolutionise the way C diff infections are treated in the clinic, in compliance with the regulatory frameworks already in place. We firmly believe that this collaboration may result in a treatment that could benefit patients, clinicians and health-care organisations alike.”

Dr Des Walsh, head of infections and immunity at the Medical Research Council, said: “Antibacterial resistance is a major and growing threat to health globally. New treatments and therapies are sorely needed. This study by Dr Clokie examines a new way to kill bacteria to circumvent resistance formation.

“She has established an impressive collection of ‘phage’ viruses and has developed strong partnerships to translate her research into potential new treatments for Clostridium difficile infection - an excellent example of moving basic experimental MRC-funded research along the development pipeline.”

 

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