The new antibiotics

They can fight infections, promise fewer side effects and can adapt when diseases resist them. Bacteriophages could be the answer to the MRSA superbug. Jerome Burne reports
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While the government invokes the spirit of Florence Nightingale in a - surely desperate - bid to tackle the growing problem of antibiotic resistance in hospitals, at least two UK biotech firms are engaged in a race to come up with a 21st century solution. Both companies are also using a rather elderly technique - discovered during the First World War - but bringing it up to date with modern genetics.

While the government invokes the spirit of Florence Nightingale in a - surely desperate - bid to tackle the growing problem of antibiotic resistance in hospitals, at least two UK biotech firms are engaged in a race to come up with a 21st century solution. Both companies are also using a rather elderly technique - discovered during the First World War - but bringing it up to date with modern genetics.

The winner will be the first to market an antibacterial product containing a type of virus know as a "bacteriophage" - literally "bacteria eater". First discovered in 1917 by the Frenchman Felix d'Herelle, "phages" were used to treat conditions like infected wounds, ulcers, typhoid and cholera for about 20 years but then, on the advent of antibiotics, were forgotten in the West.

But phages are generating huge interest in research labs because, being alive, they are able to mutate, making it much harder for bacteria to develop resistance to them. A recent study in Science found that the phage that attacks Bordetella, which causes whooping cough, can make billions of variations in a key protein. Such versatility makes resistance unlikely.

Something new is certainly needed. A few years ago the first original antibiotic compound for 35 years was introduced. Within two months resistance to it had developed.

At least two of the companies in the race are working on phages to target MRSA (methicillin-resistant Staphylococcus aureus) the main bacterium involved in hospital-acquired infections that kill at least 5,000 people a year.

Each phage only infects a specific strain of bacteria, avoiding the carpet-bombing approach of antibiotics, which knock out friendly gut bacteria as well. Phages are also everywhere - probably the most numerous life form on the planet; a millilitre of water from a river will contain about 200 million of them. "We've patented a way of collecting phages from the wild," says Nick Housby of Novolytics, one of the companies in this race. "If a new, resistant strain of MRSA emerged in hospitals we could have a phage to attack it within a matter of weeks," he adds.

At least they could in maybe three or four years time, when their cocktail of about eight different phages, one for each of the main resistant strains of MRSA, has passed all the trials. Their first product will be a nasal spray to kill off the MRSA that 30 per cent of people carry harmlessly in their respiratory system, but which can be deadly to people with weakened immune systems in hospital.

Although still fairly novel in the West, phages have long been used in Russia. Phage-impregnated bandages were widely used by Soviet troops. One refugee from the main bacteriophage research and production lab in Georgia is now heading an American company called Intralytix. Recently the company obtained the first licence for the commercial use of phages on animals to combat listeria, which contaminates food and can seriously affect pregnant women, newborns, and adults with weakened immune systems.

Phage-based treatments are still sold over the counter in some eastern-European countries, their use supported by years of clinical experience, although little of it backed by conventional trials. The only detailed account of their use was published by the Polish Academy of Sciences, which summarised the effectiveness of phage therapy on 550 patients in 10 hospitals who were suffering from serious conditions such as septicaemia, abscesses, broncho-pneumonia and fistulas. The reported recovery rate was 94 per cent.

Such reports cut little ice with the UK regulatory authorities, so the race is on to do the first clinical trial with humans using phages, not just in the UK but anywhere in the West. Those at a firm called Biocontrol believe they are the front runners. "Some time in the next few months we will be placing a phage solution in the ears of patients who have become infected following surgery," says the chief scientific officer of the company, Dr David Harper.

The bug they are targeting is called Pseudomonas aeruginosa which is responsible for, among other things, chronic ear infections and the clogging mucus found in the lungs of people with cystic fibrosis. "We've already run a successful trial on 10 dogs who had failed several rounds of antibiotic treatment," says Harper.

But perhaps the most ingenious new phage line is coming from a firm called Phico Therapeutics. "While I was working in the States some years ago I discovered this protein that is able to totally shut down a bacterium's DNA," says Heather Fairhead, the founder of the company. "The protein is only found in a species of bacterium that forms spores when food supplies run low," she explains. "It goes into a kind of suspended animation and all its DNA becomes inactive." In Fairhead's system the phage is only used as a delivery vehicle - "its one aim in life is to target bacterial DNA, so it's perfect". The first application will be a barrier cream for potential MRSA carriers in hospitals.

Sales of a successful product could be huge, and the rivalry between the contenders is hotting up. "I should point out that we aren't using any genetic modification in our product," Housby of Novolytics e-mailed me "and our phages keep on reproducing, which Phico's don't. Fairhead was equally keen to stress her rivals' shortcomings. "When you kill bacteria using wild phages," she explained "they make the bacteria burst, so toxins get spewed out, along with genetic material that can carry resistance."

It's to sort out such possible issues that the trials need to be done. For instance, although there should be no problems putting phages into creams or ointments, some experts worry about putting them directly into the body. "There's the possibility of the phage being mopped up by the immune system or causing an allergic response," warns Geoffrey Hanlon of Brighton University.

There is a nice symmetry about the notion that an alliance between the principles of Florence Nightingale and a revamped bit of Russian health care may eventually roll back the advancing bacterial hordes.

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