New antibiotic cures disease by disarming pathogens, not killing them

Oct 02, 2012

A new type of antibiotic can effectively treat an antibiotic-resistant infection by disarming instead of killing the bacteria that cause it. Researchers report their findings in the October 2 issue of mBio, the online open-access journal of the American Society for Microbiology.

"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," says Brad Spellberg of the UCLA Medical Center and David Geffen School of Medicine, a researcher on the study.

are badly needed for treating infections with the , a pathogen that most often strikes and immune- compromised individuals through open wounds, breathing tubes, or catheters. The bacterium can cause potentially lethal . 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 it was possible to mitigate the potentially lethal effects of the bacterium by blocking one of its 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," says Spellberg. This pinpointed a new therapy target for the researchers: the endotoxin these bacteria shed in the body.

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

Spellberg says 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. Molecules like LpxC-1 that inhibit rather than kill bacteria wouldn't pass muster with traditional antibiotic screens that are based on killing effectiveness.

Liise-anne Pirofski of the Albert Einstein College of Medicine and a reviewer of the study for mBio® says neutralizing virulence factors is showing a lot of promise as an alternative route for treating infections. "There's a growing movement in infectious disease therapy to control the host inflammation response in treatment rather than just 'murdering' the organism," says Pirofski. "This is a very elegant and important validation that this approach can work – at least in mice."

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ziphead
1 / 5 (3) Oct 02, 2012
Antibiotic that works agains a particilar bacterial genus? Talk about slicing it thin... the pharma wins all the way.

If you are happy to be that specific in targeting, you might as well turn to phage therapy which is already researched well. Too bad it was all done by Russians.
despinos
1 / 5 (1) Oct 02, 2012
I see a potential problem in this approach: The bacteria are allowed to multiplicate in the body.
What will happen to the organism when the compound that blocks the "virulence factors" is no longer there, for whatever the reason? Wouln'dt it mean a sudden massive production of these same "virulence factors" by a large population of bacteria?
If so, it would be Ethically doubtful to administer a medicin, that, if retired, would bring a sudden drastic appereance of the negative effects caused by the bacteria. I would see it fit as a side treatment to one that actually kills the bacteria
Bascule
not rated yet Oct 02, 2012
I see a potential problem in this approach: The bacteria are allowed to multiplicate in the body.
What will happen to the organism when the compound that blocks the "virulence factors" is no longer there, for whatever the reason? Wouldn't it mean a sudden massive production of these same "virulence factors" by a large population of bacteria?


It's quite a good question and not answered in the article. However you have to remember that the patient's immune system is still going to be operating as normal (hopefully). The immune system will mount a growing challenge to the bacteria. And because this treatment blocks the effect of the bacteria the patient won't die in the meantime.
Also since this treatment isn't doing the immune systems job it's possible that this type of treatment won't have all the same bad affect as normal antibiotics.
Bascule
3.7 / 5 (3) Oct 02, 2012
If you are happy to be that specific in targeting, you might as well turn to phage therapy which is already researched well. Too bad it was all done by Russians.


Too bad you're too lazy to learn Russian, translate their research and revitalize this Phage therapy. Still at least you have the internet to play on.
tadchem
not rated yet Oct 02, 2012
LpxC-1 doesn't kill the bacteria, it just 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.


It would seem the lethality lies not in the bacterium but in the immune system's response to its activity. In many deadly human diseases the damage is done by inflammation: arthritis, asthma, rheumatism, etc.
This would seem to be a more tactical target for research.