New antibiotic disarms pathogens

Researchers have found a new class of antibiotics that can treat an infection by disarming bacteria that cause an antibiotic-resistant infection instead of killing them.

Brad Spellberg, a researcher with the UCLA Medical Center, and the rest of his team found that it was possible to alleviate the potentially lethal effects of the Acinetobacter baumannii bacterium in laboratory mice by blocking one of its toxic byproducts instead of killing it.

A. baumannii is a pathogen that most often attacks immune-compromised individuals or hospital patients through catheters, breathing tubes or open wounds. The bacterium can lead to potentially deadly bloodstream infections and is resistant to a wide range of antibiotics.

"Traditionally, people have tried to find antibiotics that rapidly kill bacteria," Spellberg said. "But we found a new class of antibiotics which has no ability to kill Acinetobacter that can still protect, not by killing the bug, but by completely preventing it from turning on host inflammation."

The researchers used the LpxC-1 molecule to prevent the bacteria from synthesizing the deadly lipopolysaccharide endotoxin.

"We found that strains that caused the rapidly lethal infections shed lipopolysaccharide (also called LPS or endotoxin) while growing," Spellberg said. "The more endotoxin shed, the more virulent the strain was."

The molecule didn't kill the bacteria, it simply stopped the body from mounting the inflammatory immune response that actually causes the death in patients who are seriously ill.

The results of the study demonstrate the importance of finding new, physiologically relevant ways to screen potential antibiotics for pathogens that are highly resistant, according to the authors. The LpxC-1 molecule would not pass most antibiotic screens, since they are typically based on bacteria killing effectiveness.

The scientists published their findings in Tuesday's issue of mBio.