Anti-Infective Spurs Natural Defenses

A new anti-infective peptide helps mice ward off a wide range of bacteria in a roundabout way.

The synthetic peptide, called IDR-1 for innate defense regulator, doesn't target the bacteria directly. Instead, it alters the natural immune response in mice and protects them from a variety of bacteria, including some of the "superbugs" such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci that cause infections in hospitals (Nat. Biotechnol., DOI: 10.1038/nbt1288). Because it doesn't act directly on the bacteria, the peptide may not cause bacterial resistance.

Researchers at the University of British Columbia and Inimex Pharmaceuticals, both in Vancouver, started with natural peptides that are known to modulate the immune system but are also toxic and stripped them down to eliminate the toxic effects. IDR-1 protects mice from bacterial infection whether it is administered before or after infection, says microbiology professor Robert E. W. Hancock, who led the research. The peptide appears to recruit and activate monocytes and macrophages, which are immune cells that eliminate bacteria. Also a key part of the protective mechanism is the suppression of proteins that trigger inflammation, including tumor necrosis factor α and interleukin-6.

The work is a "major breakthrough in anti-infective agent research," says William M. Shafer, a microbiologist at Emory University School of Medicine. "Although I have become somewhat jaded over the years regarding anti-infective research programs that show initial promise with a particular compound, I am cautiously optimistic about the future success of IDR-1."

Immunologist Michael A. Zasloff of Georgetown University isn't so sure. "There is no clear target, and the mechanism of action is not clear," he says. "As a consequence, it becomes difficult if not impossible to transfer the technology to man."