Rise and rise of the superbug

Barry Nelson reports on desperate efforts centred on the North-East to find new ways to kill potentially deadly bacteria.

IT will be another three months before Durham University's new bugbusting lab will be ready for action - and it can't come a day too soon. Professor Adrian Walmsley, the university's new chair in infectious diseases, reckons that superbugs are evolving so rapidly that effective antibiotics probably only have ten years of useful life left.

That's why he has moved to the North-East from Glasgow University to lead a team of scientists who hope to find new ways to kill potentially dangerous bacteria.

Technicians are currently fitting out the £250,000 new laboratory which will be used to study organisms such as MRSA (Methicillin Resistant Staphylococcus Aureus) and drug-resistant strains of Mycobacterium Tuberculosis, or TB.

The secure lab, which is designed to prevent the escape of drug-resistant bacteria into the environment, should be ready in early March. Once it goes "live" it will join other teams of scientists around the world who are urgently seeking new ways to defuse the ticking time-bomb of drug resistant bacteria.

Antibiotics have been around since penicillin was first introduced in 1941 and a whole family of drugs have subsequently been developed. But, paradoxically, as each new drug is introduced, the micro-organisms which cause bacterial disease have changed and mutated to avoid being destroyed.

As the years have passed and the use of antibiotics has become more widespread and indiscriminate, this has speeded up the process of drug resistance.

While the NHS now urges patients to think twice about asking for antiobiotics when they visit their GP, scientists believe it is probably too late. The nightmare scenario of patients fighting for life against the effects of drug-resistant bugs while doctors can only watch helplessly is already with us.

Only last week the Public Health Laboratory Service reported that deaths from MRSA in England and Wales had seen a steep increase between 1993 and 1998.

In death certificates which gave staphylococcal infection as the underlying cause of death, the proportion mentioning MRSA increased from eight per cent in 1993 to 44 per cent in 1998.

The report stated that drug resistance probably had an impact on the success of medical management of many of these cases and urged further improvements in infection control in hospitals.

But stepping up handwashing and isolating infected patients may not be enough if present trends continue. Prof Walmsley says aside from drug-resistance, some bugs are already developing mechanisms to resist common detergents and cleaning fluids used in the NHS.

If drug resistance becomes much more common - which many experts predict - then mankind, let alone the NHS, has a major fight on its hands.

For Prof Walmsley the competition between bacteria which prey on mankind and our ability to keep superbugs in check is a neck-and-neck race.

At the moment we are slightly ahead of the game, but within a decade the drug-resistant strains of bacteria could close the gap. And unless a new generation of antibiotic drugs can be developed within the decade, the superbugs could have the upper hand.

"We are in a constant battle trying to beat the bacteria. We have so many weapons in our arsenal of drugs but as we use them on organisms, the organisms change and evolve," he says. "A bacterium such as E coli takes 30 minutes to replicate, which means it can change its genetic code very quickly. When it does it can mutate so that the old drugs are no longer effective."

Prof Walmsley argues that the pharmaceutical industry has only recently woken up to the frightening prospect of being outflanked by drug-resistant bacteria.

"Really the industry has not invested in producing new antibiotics. They put most of the money into antivirals, chemotherapy and genetic diseases because those are diseases that people get in developed countries, whereas a lot of infectious diseases are found in developing countries," he says. "But now, with people travelling all around the world, these diseases can easily be spread. What could be a problem in the developing world today could be a problem here tomorrow."

Prof Walmsley is particularly interested in opening up a new line of attack against superbugs. One promising area is the possibility of finding ways to disable a protective mechanism developed by bacteria.

Sometimes compared to the bilge pump of a ship, this mechanism is activated when a toxic drug penetrates the membrane of the bacteria.

Prof Walmsley explains: "As the antibiotic drug is diffusing into the bacterial cell, it produces protein pumps within the membrane and it uses them like bilge pumps to continuously pump out the antibiotic so it is no longer toxic."

"These pumps are particularly worrying because they don't just pump one drug - they can pump out a whole range of drugs and acquire resistance to drugs they have never encountered."

The Stockton campus team, based in the impressive new Wolfson Institute building, will concentrate on trying to find out more about how this pump mechanism works. What makes this particularly difficult is that the pump mechanism represents only 0.1 per cent of the proteins making up the cell membrane.

"We will try to increase them so they may be up to 20 per cent of the cell membrane. Once you have got the bacteria to over-produce these pumps, you have to extract them from the membrane, hopefully in a functional form," says Prof Walmsley.

The Stockton team would then try to study the pump mechanism by means of a process known as crystallography. "We need to do this to determine the structure and function of these pumps," says the professor.

If the team can work out how the mechanism works, they may be able to devise a method of blocking this process. It sounds relatively straightforward but Prof Walmsley points out that it is only within the last few weeks that anyone in the world had been able to produce a crystallised image of such a pump - and that was in the elite scientific journal Nature. "That is useful information but that is only one of a set of pumps. Each organism is different," he says.

The team also plans to study a similar defensive pumping mechanism used by the bacteria that causes TB. "The TB bacterium uses this pump to cover itself with a waxy substance which cannot be penetrated by a lot of antibiotics," says Prof Walmsley.

"We are not working with the organism itself, we are working with the DNA. It doesn't use it at the moment for pumping out antibiotic drugs but it could in future. We are interested because it is a potentially good target. It has been shown that if you knock out this pump, they are less virulent. We could perhaps block this mechanism which would stop them pumping out this waxy substance."

The work is just beginning on the banks of the Tees but it's a race against time in the hope that mankind can stay one step ahead in this potentially deadly game.