New antibiotic may fight resistant germs

updated 1:42 p.m. ET May 17, 2006

NEW YORK - Researchers have found a potentially valuable new antibiotic in a scoop of soil from South Africa.

Using a novel screening technique, scientists from Merck & Co. have found a chemical compound that is effective against germs that have developed resistance to existing antibiotics. The discovery could provide a vital weapon in the ongoing battle against infectious bacteria, which are constantly evolving defenses to the drugs used against them.

“We need to continuously find antibiotics,” said Sheo Singh, Merck’s director of natural products chemistry.

With the recent emergence of “superbugs” that are resistant to even the most potent antibiotics, there is a very real possibility that in the near future some infections will simply be incurable.

Part of the problem is that most antibiotics are just modifications of drugs that have been around for half a century. Another part of the problem is that despite all the recent advances in genetics and molecular biology, the hunt for new antibiotics is still conducted by trial and error.

Genetic trick
The Merck researchers addressed both problems with a clever genetic trick that made an existing drug-hunting process more effective and also targeted novel types of antibiotics.

Their innovation was to test extracts of fungi, plants and other natural substances against bacteria with a genetically engineered Achilles’ heel. Because the bacteria were weakened, any compound that harmed them would have a more dramatic effect and thus be easier to identify.

The Merck scientists also chose the genetic handicap carefully, placing it in a metabolic pathway that is not attacked by any major existing antibiotics. That increased the likelihood that any promising compound they discovered would be something for which the bacteria had not yet developed a resistance.

“We screened over 250,000 extracts that came from things isolated all the way around the world,” said Merck scientist Stephen M. Soisson.

One of them, platensimycin, showed exceptional promise. And when tested in mice infected with a common and troublesome strain of Staphylococcus aureus, it proved highly effective.

The Merck scientists report their discovery in the current issue of the journal Nature.

“I’m guessing that this is a very promising molecule,” said Eric D. Brown, a biochemist at McMaster University in Hamilton, Ontario, though he noted that most potential compounds never reach the pharmacy.

Of course, even if platensimycin turns out to be a clinically useful antibiotic, bacteria will inevitably become resistant to it just as they have existing drugs.

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