Navigation Links
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 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.


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

Related biology news :

1. Cholesterol-lowering drugs and the effect on muscle repair and regeneration
2. Vitamin C supplements may reduce benefit from wide range of anti-cancer drugs
3. Discovering drugs, biofuels in tropical seas
4. Academy participates in project to discover drugs, biofuels in tropical seas
5. European researchers harness unique properties of boron to develop new drugs and diagnostics
6. Self-assembling nano-fiber gel delivers high concentrations of clinically approved drugs
7. Moderate use averts failure of type 2 diabetes drugs in animal model
8. Montana State University researchers find gene that regulates molds resistance to drugs
9. MSU researcher studies ties between cholesterol drugs, muscle problems
10. New technique eliminates toxic drugs in islet transplant in diabetic mice
11. REGiMMUNE receives $12 million in grants to develop transplant and allergy drugs
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/23/2017)... and ITHACA, N.Y. , June 23, ... University, a leader in dairy research, today announced a ... to help reduce the chances that the global milk ... of this dairy project, Cornell University has become the ... the Food Supply Chain, a food safety initiative that ...
(Date:5/6/2017)... -- RAM Group , Singaporean based technology ... biometric authentication based on a novel  quantum-state ... perform biometric authentication. These new sensors are based on a ... Group and its partners. This sensor will have widespread ... security. Ram Group is a next generation sensor ...
(Date:4/13/2017)... , April 13, 2017 UBM,s Advanced Design ... will feature emerging and evolving technology through its ... Summits will run alongside the expo portion of the ... panels and demonstrations focused on trending topics within 3D ... design and manufacturing event will take place June 13-15, 2017 ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... ... October 11, 2017 , ... ComplianceOnline’s Medical Device Summit is back ... 8th June 2018 in San Francisco, CA. The Summit brings together current and former ... CEOs, board directors and government officials from around the world to address key issues ...
(Date:10/11/2017)... BioMarketing, a leading provider of patient support solutions, has announced ... network, which will launch this week. The VMS CNEs will ... to enhance the patient care experience by delivering peer-to-peer education ... professionals to help women who have been diagnosed and are ... ...
(Date:10/11/2017)... ... October 11, 2017 , ... Disappearing forests and increased emissions are the ... million people each year. Especially those living in larger cities are affected by air ... one of the most pollution-affected countries globally - decided to take action. , “I ...
(Date:10/11/2017)... ... October 11, 2017 , ... Singh Biotechnology today announced ... to SBT-100, its novel anti-STAT3 (Signal Transducer and Activator of Transcription 3) B ... to cross the cell membrane and bind intracellular STAT3 and inhibit its function. ...
Breaking Biology Technology: