Bacteria offer lessons to drug makers

Science News, Dec 18, 1999 by J. Raloff

Many bacteria produce poisons that slay microbial competitors while leaving their friends and family--and people--unharmed. In probing one such toxin, scientists believe they've uncovered clues that could lead to better antibiotic drugs.

The toxin they focused on, nisin, belongs to a group of small proteins known as bacteriocins. Food scientists routinely make cheeses and yogurts using starter cultures containing bacteria that produce nisin. As the microbes grow, nisin protects these products from germs causing spoilage or food poisoning, including those responsible for botulism and listeriosis (SN: 2/7/98, p. 89).

Though nisin's germicidal prowess was discovered 71 years ago, the means by which the protein kills bacteria has remained a mystery. In the Dec. 17 SCIENCE, Dutch and German researchers reveal new clues to nisin's potency.

In a series of experiments, Eefjan Breukink of Utrecht University in the Netherlands and his colleagues have demonstrated that the bacteriocin targets an oily substance known as lipid II. Produced inside bacteria, lipid II ferries a pair of sugars through the bacterial membrane to sites where they become building blocks for the microbes' outer cell wall.

By attacking lipid II, Breukink explains, nisin unleashes a double whammy. It not only disables the lipid, an action that alone can kill bacteria, but also creates pores in the cell membrane through which vital ions hemorrhage. This combination of independent effects on lipid II explains nisin's power, Breukink says. In his team's tests, nisin was 1,000 times as toxic to target bacteria as was magainin, a natural antibiotic produced in animals (SN: 3/18/95, p. 166).

"We now need to know exactly where nisin binds to lipid II and what part of nisin binds it," he says. Such knowledge, he maintains, could lead to novel antimicrobial drugs. They're needed to cope with the growing resistance of bacteria to current antibiotics (SN: 6/5/99, p. 356).

Nisin's targeting of lipid II "is a breakthrough finding that sheds totally new light on many aspects of bacteriocin action," says Thomas J. Montville of Rutgers University in New Brunswick, N.J.

The finding indicates that nisinlike compounds "could have important pharmaceutical applications," adds Todd R. Klaenhammer of North Carolina State University in Raleigh. Not only are bacteriocins too small to trigger allergic reactions, but they're also very selective, he notes. That means they can be unleashed against an infectious agent without fear that they would also kill microbes beneficial to a person.

While Montville agrees, he still "would really hate to see [bacteriocins or synthetic versions] used in medicine" because work by several labs, including his own, shows that bacteria develop resistance to these substances. "We have many serious bacterial problems in foods," he notes, arguing that bacteriocins therefore should be reserved for fighting spoilage and food poisoning.

"Though they remain a big gun for protecting foods," he asserts, "they would only become another BB shooter in the medicinal arsenal."