Dec. 16, 1999 (Urbana, Ill.) -- Researchers may have finally found an Achilles' heel for some antibiotic-resistant bacteria, and the results could lead to a new class of antibiotics that kill these dangerous bugs, according to results reported in the Dec. 17 issue of the journal Science.
Low doses of a food preservative called nisin Z kill bacteria by binding to a component of their cell membrane and poking holes in the cell, and the bacteria seem unable to evolve ways to fend off the drug the way they sometimes fend off conventional antibiotics, the authors say.
Nisin Z, which is produced by Lactococcus lactis, a species of bacteria found in milk and cheese, has been used as a food preservative for almost 50 years. That's because even low doses of it can kill bacteria that contaminate food, and researchers have long known that it is nontoxic to humans. But until recently, researchers knew little about how it killed bacteria, study co-author Eefjan Breukink, PhD, tells WebMD. Breukink is a postdoctoral fellow at Utrecht University in the Netherlands.
The researchers were particularly curious why nisin Z was so much more toxic to bacteria than other molecules with similar chemical structures. Nisin Z is a member of a class of molecules called peptides, which are small protein-like molecules. In recent decades, several peptides had been found to kill bacteria, but nisin Z was much more potent than other antibacterial peptides that had been studied, Breukink says. "The real question was why is nisin so active as compared to other types," he says.
The researchers already knew that nisin Z formed holes in bacterial membranes, but they didn't know how. To find out, they compared how well nisin Z poked holes in bacterial membranes as opposed to in artificial membranes. Nisin only worked well in true membranes, suggesting that the artificial membranes were missing a key component, Breukink says.
That missing component was a fatty molecule called lipid II. The authors showed that nisin Z can't bind to membranes and poke holes when the membranes are treated with the potent antibiotic vancomycin, which blocks nisin Z from contacting the lipid II. "That was the key experiment," Breukink says.
"This report helps us understand why nisin has such excellent activity," Donald Low, MD, tells WebMD in an interview seeking an independent view of the research. Low says that's important because now that they know how nisin Z works, pharmaceutical chemists can design variants that could be even more effective than nisin Z. Low is the chairman of the microbiology department at the University of Toronto.
"The take-home message is that we have a compound that has prevented the growth of bacteria in food products for years without the development of resistance. We finally understand that," Low says. The next goal is to "use that to treat infections in humans."
But he and other researchers warn that it will take years of research before the discovery can be parlayed into a new drug to treat antibiotic-resistant bacteria. For example, they'll have to determine the detailed molecular structure of nisin Z as it sits on the surface of the cell; they'll have to enlist teams of chemists to come up with related molecules; and they'll have to test the safety of the new compounds in clinical trials, says Steve Projan, PhD, director of antibacterial research at Wyeth-Ayerst Laboratories Inc. in Pearl River, N.Y. "This has long-term implications, but there is not yet a drug on the horizon based on this discovery," he says.
- A food preservative that has been used for more than 50 years, called nisin Z, could one day be used as a potent antibiotic in humans.
- Nisin Z works by binding to the cell membrane of bacteria and poking holes in the cell.
- Scientists now know how nisin Z works to kill bacteria, but it will be years before a drug could be developed based on this knowledge.