This 2007 Scientific American article reports on experiments using short proteins, or peptides, to attack deadly antibiotic-resistant "superbug" bacteria such as staph (MRSA). Source: Scientific American, March 25, 2007.
New Protein Fights Superbugs by Boosting Immune System
When antibiotics have lost their oomph, kick the immune system up a notch.
By JR Minkel March 25, 2007
How do you fight deadly bacteria that shrug off modern antibiotics? Simple: juice up the immune system to fight its own battles. Researchers have come up with a new compound that activates the immune system's first line of defense. Mice that received the chemical were less likely to succumb to drug-resistant staph or other infections. The group speculates that the drug could make such infections receptive to antibiotics again.
Antibiotic-resistant bacteria sicken about two million people and kill 90,000 every year in North America, says immunologist Robert Hancock of the University of British Columbia. Among the most dangerous are vancomycin-resistant Enterococcus (VRE) and methicillin-resistant Staphylococcus aureus (MRSA), which are difficult to treat with common antibiotics. Looking for new ways to attack these so-called superbugs, Hancock studied a group of short proteins, or peptides, that in high concentrations can kill bacteria.
Concerned that the peptides might trigger sepsis, a potentially lethal condition brought on by bacteria in the bloodstream, Hancock administered them to infected mice. "What we found, in contrast, was they actually reverse sepsis," he says. The only trouble was that they also caused allergylike reactions and killed healthy intestinal cells. So he and his colleagues engineered shorter peptides that they hoped would prevent sepsis without causing other complications.
They hit on a 13-amino-acid peptide, which they call an innate defense regulator (IDR-1). To test it out, they injected mice with IDR-1 either one to two days before or four hours after infecting them with VRE, MRSA or Salmonella. The treated mice were nearly twice as likely to survive infection, the group reports this week in Nature Biotechnology.
Hancock, who co-founded a company to commercialize IDR-1, says the peptide does not kill bacteria directly. Instead it seems to prime the body's quick and dirty immune response, called innate immunity. A subsequent infection, he says, may then flag the body to send a surplus of white blood cells called monocytes and macrophages to gobble up invading pathogens, but fewer of the more aggressive neutrophils, which are more likely to induce sepsis.
Hancock says that clinical trials of IDR-1 could begin in 12 to 15 months. He adds that preliminary evidence suggests that the peptide can enhance the effectiveness of antibiotics in mice, even against superbugs such as VRE.
Staph, Infection, Bacteria, Antibiotic, Drug-Resistant, MRSA, Staphylococcus Aureus, Superbug, Short Protein, Peptide, Sepsis, Amino Acid, White Blood Cell, Immune System, Immunity, Scientific American, “Chemistry Now”