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Experts: Chatter key to fight superbugs
2007-02-01
Do germs communicate? Many scientists think so and are betting the chatter may hold the key to developing the next generation of drugs to fight killer superbugs. The conventional wisdom has long been that the carpet-bombing approach is the best way to fight infection. But as evidence of bacterial bonding has mounted in the past decade, researchers are now focusing on antibiotics that will break down the lines of communication. In the last 20 years, the number of scientists working in this field has jumped from a few solitary researchers to thousands. In Britain, the strategy is one of the top research priorities of a newly formed center dedicated to stopping superbugs. "Bacteria are a bit like an army going into battle," said Dr. Paul Williams, professor of molecular biology at the center at Nottingham University. "Only when they've got strength in numbers do they tell their troops to start firing." The thinking is that if bacterial communication can be interrupted, the microbes might be incapacitated before doing any damage. And by not killing off the bacteria, they won't have the Darwinian opportunity to evolve into resistant strains. Scientists are still years away from producing a commercially available drug. But if the strategy proves successful, it could open the way for new weapons against superbugs such as the deadly MRSA superbug -- whose infection rate has jumped dramatically in the last two decades. Researchers refer to the bacterial communication system as "quorum sensing." Just like in a company boardroom, a quorum is needed before any major action can be taken. Bacteria communicate with each other by sending out a chemical signal that is in turn picked up by special receptors. Williams and his colleagues are developing enzymes to destroy the signal molecules. Experts are also trying to break into other bacterial social activities. For instance, bacteria congregating to form a "biofilm" achieve a type of super-resistance. "If we can break them up, we can kill them," said Dr. Pete Greenberg, a microbiology professor at the University of Washington. Greenberg is working on methods to disable a bacteria that frequently attacks people with cystic fibrosis. New strategies to fight bugs that don't end up boosting their immunity would be a big boost. Pharmaceuticals companies have been reluctant to invest in traditional antibiotics because many germs can develop resistance within months. The last new classes of antibiotics appeared in the 1990s. "With only one or two antibiotics that are effective against a major pathogen, we are potentially living on borrowed time," warned Dr. Richard James, director of Britain's newly established Centre for Healthcare Associated Infections at Nottingham University. "Unless we do something to change the situation, we are facing a post-antibiotic apocalypse." James, who is not involved in quorum sensing research, believes that it is one of the most promising avenues to developing new antibiotics. "Perhaps the answer to the problem of increasing bacterial resistance is for us to be even more clever than the bacteria," he said. "We could do this if we have antibiotics that disable the bacteria, which may then allow the host's immune system to kick in." Still, there are no guarantees that antibiotics based on quorum sensing will work. For instance, it's uncertain if knocking out communication lines in later stages of an infection would have any impact. "There are no experiments to show that in a raging infection, a quorum sensing inhibitor could calm it down," said Greenberg. "It might already be too late by the time patients turn up with an infection." But with no new antibiotics on the horizon, scientists say new strategies must be attempted. "Drugs that inhibit quorum sensing are in the unproven category, but there is still a possibility they could work," said Dr. Anthony Coates, a professor of medical microbiology at St. George's Hospital Medical School in London. "Quorum sensing might produce very effective antibiotics, but they might only work on specific species of bacteria," he said, adding that further tests on existing compounds is needed. "The cupboard is running bare, and without any new antibiotics, we have to keep trying."
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