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New research shows promise for anti-virulence drugs

October 31st, 2011
by Tania

New laboratory simulations suggest anti-virulence drugs can fight infection, without bacteria developing resistance.

Anti-virulence drugs are considered to hold the potential for the treatment of infections as unlike antibiotics they disarm rather than kill pathogens. This in theory helps overcome the issues with resistance, by simply neutralising virulence factors rather than destroying the pathogen.

The new study, published in the online journal mBio, offers evidence that if these anti-virulence drugs are applied in the right way they can indeed produce this effect. Using laboratory simulations, the researchers from Oregon State University created a microcosm that simulates an infection, and introduced bacteria which employ quorum sending, allowing their attack on the body to be coordinated for the greatest effect.

Many bacterial pathogens use quorum sensing to control the making of their virulence factors.

Sam Brown, of Edinburgh University, Invited Editor on the study, explained: "It's a very important demonstration of the principle that social effects can slow or even halt the spread of resistance to anti-virulence drugs."

Surrogates were used to overcome the challenges with creating a strain resistant to anti-virulent drugs. "It's kind of a role-playing exercise. They used bacteria that behave as we expect drug-resistant bacteria might behave," Mr Brown added.

Sensitive mimics, without the ability to cooperate, and resistant mimics were tested to see if the resistant strain could proliferate in an infection. The team observed that the sensitive mimics exploit the quorum sensing of the resistant drugs in an effort to get ahead, which slows the growth of the bacteria. From this, they concluded any resistance from an anti-virulence drug would not spread, although Mr Brown said there is reason to be cautious.

"I think these drugs are promising, even if we do anticipate resistance, because they can slow the rate of resistance evolution, much slower than the rate of resistance evolution to traditional antibiotics," he concluded.

Research previously revealed Salmonella has an anti-virulence pathway, which could be exploited to develop a vaccine for the disease. When this pathway is knocked out, the Salmonella becomes ten times more virulent, the study published in the Public Library of Science show, although this only happens once the pathogen enters the intestine. 

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