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Can antivirulence drugs stop infections without causing resistance?
Date:10/10/2011

Antivirulence drugs disarm pathogens rather than kill them, and although they could be effective in theory, antivirulence drugs have never been tested in humans. A new study to be published in the online journal mBio on Tuesday, October 18 reveals these drugs have the potential to fight infection while avoiding the pitfalls of drug resistance.

Traditional antibiotics aim to kill or stop the growth of pathogens, but antivirulence drugs prevent disease by neutralizing virulence factors, the specific proteins or toxins that a pathogen uses to establish an infection. Scientists have long thought such a strategy could prevent pathogens from developing drug resistance, since antivirulence drugs don't kill the pathogens that are susceptible and leave a wide opening for the few resistant organisms that may be left. Thus, in theory, antivirulence drugs don't offer much benefit to the pathogens that get around the drug. However, these ideas have never been tested.

The study coming out this week provides evidence that antivirulence drugs have the potential to suppress resistance if they are applied in the right way. Brett Mellbye and Martin Schuster from Oregon State University carried out laboratory simulations to determine the effect antivirulence drug-resistant strains could have on therapy. They found that in pathogens that rely on cell-to-cell communication and cooperation, resistant strains will not overtake sensitive strains, allowing antivirulence therapies that target social interactions to work even when resistance arises.

"It's a very important demonstration of the principle that social effects can slow or even halt the spread of resistance to antivirulence drugs," says Sam Brown, of Edinburgh University, Invited Editor on the study. "Their results align with our understanding of social evolution."

Mellbye and Schuster created a microcosm that simulates an infection, says Brown, and they used bacteria that employ
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Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology
Source:Eurekalert

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