New antibiotics discovered that could beat back superbacteria
Researchers hope to stop virulent form of staph
By LEE BOWMANSCRIPPS HOWARD NEWS SERVICE
Researchers reported Friday they have found four promising antibiotics in chemical families never used before against germs through a novel testing tool that can screen dozens of compounds at once.
The four compounds appear to kill bacteria, at least in a lab dish. Because they probably attack bacteria in different ways, germs should take some time to develop resistant strains.
"These represent whole new classes of antibiotic agents," said Helen Blackwell, lead author of a University of Wisconsin-Madison report on the discoveries published in the journal Chemistry and Biology.
Also, while the most potent compounds were able to kill several dangerous strains of bacteria, the strongest activity was against a highly drug-resistant strain of staph infection (Staphylococcus aureus) that has been plaguing hospitals for years and has recently become common in community settings.
"Strains are emerging that are drug-resistant to all known antibiotics," Blackwell said. "This is not a problem that is going to go away, and actually it's going to get worse. There's a sense of urgency."
The best approach is to be able to hit bacteria with drugs they have not seen before. But finding a potentially useful drug against a broad spectrum of germs is not much different from finding a needle in a haystack.
Blackwell's team designed a way to sift through a lot of hay at once with a device it calls a small-molecule macroarray. The scientists synthesize molecules on a flexible, paperlike sheet, building a compound from the bottom up by adding ingredients to the sheet one at a time.
Each array has dozens of compounds arranged in grids of dots that are about the size of a pencil eraser.
They put each array up against a battery of germs, testing the potency of each compound against various bacterial strains.
The whole process of building and testing a batch of 50 to 300 compounds takes about two days.
Only about 2 percent of the compounds tested using the arrays show any potential against bacteria. And that's just a first step on a long path to drug development.
The next stage is to understand how the compounds work to kill bacteria. "What features of compounds are necessary for activity, and can we improve them?" Blackwell said.
Once the active elements and mechanism are understood, researchers can begin testing doses and evaluating the compounds for safety in animals and eventually humans, if trials go well.
The key is that with the new macroarray, Blackwell said it's possible to see which molecules are active fairly quickly, and "we can gather information on how to improve them fairly quickly."