Antibiotic cures disease by disarming pathogens
A new type of antibiotic can treat an antibiotic-resistant infection by disarming instead of killing bacteria.
Scientists are in a race to develop drugs that can treat infections with the bacterium Acinetobacter baumannii- a pathogen that most often strikes hospital patients through open wounds, breathing tubes, or catheters.
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.
“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 Brad Spellberg of the UCLA Medical Center.
The antibiotic shuts down the manufacture of the endotoxin
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,” said Spellberg.
This pinpointed a new therapy target for the researchers: the endotoxin these bacteria shed in the body.
Blocking the synthesis of the endotoxin with a small molecule called LpxC-1 prevented infected mice from getting sick.
Spellberg explained LpxC-1 doesn’t kill the bacteria, it shuts down the manufacture of the endotoxin and stops the body from mounting the inflammatory immune response to it that is the actual cause of death in seriously ill patients.
Spellberg believes this is a direction few researchers have taken when exploring ways to treat infections but that it could make the difference in finding an effective drug.
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, write the authors.