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

quorum sensing, a form of communication that enables the bacteria to time their attack for greatest effect. Quorum sensing is an important target for antivirulence drugs because many bacterial pathogens, including the lung pathogen Pseudomonas aeruginosa, employ quorum sensing to control the manufacture of their virulence factors.

To circumvent the problem of creating a strain that is resistant to an antivirulence drug, Brown says, the authors used surrogates. "It's kind of a role-playing exercise," to test their ideas, he says. "They used bacteria that behave as we expect drug-resistant bacteria might behave." "Sensitive" mimics are bacteria that lack the ability to communicate and cooperate. "Resistant" mimics are actually run-of-the-mill bacteria that retain the ability to "talk" amongst themselves.

The researchers pitted resistant mimics against sensitive mimics to test whether resistant strains can proliferate in an infection. The results showed that sensitive mimics cheat to get ahead: they exploit the resources that the resistant bacteria provide through quorum sensing. This delays the growth of all the bacteria, suggesting that resistance to an antivirulence drug that targets quorum sensing would not spread. The authors say this highlights the potential of antivirulence strategies that target cooperative behaviors and shared virulence factors.

Brown is optimistic but circumspect about the findings. "These results could very well stand, but in the the real world resistance could still emerge and we need 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," says Brown.


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Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology
Source:Eurekalert

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