Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Can antivirulence drugs stop infections without causing resistance?

11.10.2011
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 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.

mBio® is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online at http://www.mbio.asm.org

Jim Sliwa | EurekAlert!
Further information:
http://www.asmusa.org
http://www.mbio.asm.org

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

From rocks in Colorado, evidence of a 'chaotic solar system'

23.02.2017 | Physics and Astronomy

'Quartz' crystals at the Earth's core power its magnetic field

23.02.2017 | Earth Sciences

Antimicrobial substances identified in Komodo dragon blood

23.02.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>