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
New method uses just a drop of blood to monitor lung cancer treatment
19.10.2018 | Osaka University
Photoactive bacteria bait may help in fight against MRSA infections
12.10.2018 | Purdue University
Scientists at the Max Planck Institute for Polymer Research (MPI-P) in Mainz (Germany) together with scientists from Dresden, Leipzig, Sofia (Bulgaria) and Madrid (Spain) have now developed and characterized a novel, metal-organic material which displays electrical properties mimicking those of highly crystalline silicon. The material which can easily be fabricated at room temperature could serve as a replacement for expensive conventional inorganic materials used in optoelectronics.
Silicon, a so called semiconductor, is currently widely employed for the development of components such as solar cells, LEDs or computer chips. High purity...
Augsburg chemists present a new technology for compressing, storing and transporting highly volatile gases in porous frameworks/New prospects for gas-powered vehicles
Storage of highly volatile gases has always been a major technological challenge, not least for use in the automotive sector, for, for example, methane or...
When we put water in a freezer, water molecules crystallize and form ice. This change from one phase of matter to another is called a phase transition. While this transition, and countless others that occur in nature, typically takes place at the same fixed conditions, such as the freezing point, one can ask how it can be influenced in a controlled way.
We are all familiar with such control of the freezing transition, as it is an essential ingredient in the art of making a sorbet or a slushy. To make a cold...
Thin organic layers provide machines and equipment with new functions. They enable, for example, tiny energy recuperators. In future, these will be installed...
Das Zusammenspiel aus Struktur und Dynamik bestimmt die Funktion von Proteinen, den molekularen Werkzeugen der Zelle. Durch Fortschritte in der...
17.10.2018 | Event News
16.10.2018 | Event News
02.10.2018 | Event News
19.10.2018 | Life Sciences
19.10.2018 | Physics and Astronomy
19.10.2018 | Trade Fair News