Scientists have taken a big step towards a new generation of antibiotics by designing compounds that stop bacteria "talking to each other", thwarting their ability to spread infection. The revolutionary approach renders bacteria benign rather than killing them off, and comes as many antibiotics are losing their potency against pathogens which have developed drug resistance.
Tests showed the compounds actively blocked the spread of Pseudomonas aeruginosa, a common bacterium which causes fatal lung infections in people with cystic fibrosis and leads to life-threatening blood infections in patients with serious burns or immune system disorders such as Aids.
Colonies of bacteria use chemical signals to keep tabs on their numbers and, like an amassing army, only attack when their populations are large enough to ensure they will swamp a host's immune defences. The bacteria sense their numbers by the strength of the chemical signals they receive and as soon as they reach a certain threshold change behaviour dramatically, growing aggressively and turning on virulence genes to cause infection. Many bacterial colonies also set up defences by secreting a mucus-like substance which forms a slimy, protective "biofilm" around them, making them nearly impervious to antibiotics.
In 2002 the US National Institutes of Health estimated that up to 80% of bacterial infections spread by using biofilms. The films offer such good protection that in many cases the bacteria could be killed only by giving the patient a lethal dose of antibiotics.
Researchers at the University of Wisconsin-Madison used a new technique called microwave-assisted chemistry to design compounds called N-acylated L-homoserine lactones (AHLs). These compounds are similar to those used by bacteria, but with one important difference - when they come into contact with bacteria they act as "earplugs", in effect leaving the bacteria oblivious to their neighbours. Because their communication system is cut, the bacteria never get the signal to attack or produce biofilms.
Helen Blackwell, the head scientist for the research, said her group had used the compounds to prolong the lives of organisms infected with Pseudomonas aeruginosa, and had developed finely tuned AHLs to target specific strains of bacteria. These could be used, for instance, to prevent infection in the gut without harming healthy bacteria.
Further tests are needed to prove the compounds are capable of preventing diseases in humans. They may work best in combination with other antibiotics, by making bacteria more vulnerable.
"There is an urgent need for new antibacterial therapies," Dr Blackwell said. "The ability to interfere with bacterial virulence by intercepting bacterial communication networks represents a new therapeutic approach, and is clinically timely."
The research, which was presented yesterday at the annual meeting of the American Chemical Society, in San Francisco, raises hopes for the treatment of some of the most deadly diseases, such as tuberculosis, which infects nearly 15 million people worldwide. Last week the World Health Organisation warned that a deadly strain of TB, virtually untreatable with existing drugs, seemed to be spreading across the globe. Extreme drug-resistant TB has killed people in several countries.
The compounds designed by Dr Blackwell's team are in the early stages of development but ultimately could be used to tackle damaging crop and livestock diseases and persistent infections linked to medical implants and catheters.
Alan Larsen, director of research at the Cystic Fibrosis Trust, said: "We welcome any advances in scientific research that may speed up the development of an effective treatment for cystic fibrosis, which affects millions across the world."
