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New Antibiotic ‘Disarms’ Pathogens Without Killing Them

Researchers use molecule to block endotoxin synthesis (Oct. 2)

A new type of antibiotic can effectively treat an antibiotic-resistant infection by disarming instead of killing the bacteria that cause it, according to an October 2 announcement from the American Society of Microbiology (ASM). Researchers reported their findings in mBio, the ASM’s online journal.

“Traditionally, people have tried to find antibiotics that rapidly kill bacteria. 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,” said researcher Dr. Brad Spellberg.

New drugs are badly needed for treating infections with the bacterium Acinetobacter baumannii, a pathogen that most often infects hospital patients and immune-compromised individuals through open wounds, breathing tubes, or catheters. The bacterium can cause potentially lethal bloodstream infections. Strains of A. baumannii have acquired resistance to a wide range of antibiotics, and some are resistant to every FDA-approved antibiotic, making them untreatable.

Spelling and his colleagues found that, in laboratory mice, it was possible to mitigate the potentially lethal effects of the bacterium by blocking one of its toxic products rather than killing it.

“We found that strains that caused the rapidly lethal infections shed lipopolysaccharide [also called LPS or endotoxin] while growing. The more endotoxin shed, the more virulent the strain was,” Spelling said.

This finding revealed a new therapeutic target for the researchers: the endotoxin that A. baumannii sheds in the body.

Blocking the synthesis of the endotoxin with a small molecule called LpxC-1 prevented infected mice from getting sick. Unlike traditional antibiotics, Spellberg said, LpxC-1 doesn’t kill the bacteria; it just shuts down the manufacture of the endotoxin and stops the body from mounting an inflammatory immune response to it, which is the actual cause of death in seriously ill patients.

Spellberg said this is a direction few researchers have taken when exploring ways to treat infections, but it could make the difference in finding effective drugs. The results also highlight how important it is to find new, physiologically relevant ways of screening potential antibiotics for pathogens with a high degree of resistance, the authors wrote. Molecules such as LpxC-1 that inhibit rather than kill bacteria wouldn’t pass muster with traditional antibiotic screens that are based on killing effectiveness.

For more information, visit the ASM Web site.

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