Going "off the grid," like rogue secret agents, some bacteria avoid antibiotic treatments by essentially shutting down and hiding until it's safe to come out again, says Thomas Wood, professor in the Artie McFerrin Department of Chemical Engineering at Texas A&M University.
This surreptitious and elaborate survival mechanism is explained in the online April edition of "Nature Chemical Biology," which details the research of Wood and his post doctoral student Xiaoxue Wang along with colleagues Breann Brown, Wolfgang Peti and Rebecca Page of Brown University.
"Through our research, we're understanding that some bacteria go to 'sleep,' and that antibiotics only work on bacteria that are metabolically active," Wood explains. "You need actively growing bacteria to be susceptible to antibiotics. If the bacterium goes to sleep, the antibiotics, no matter what they do, are not effective because the bacterium is no longer doing the thing that the antibiotic is trying to shut down."
It's an alternative method for survival, Wood says, that starkly contrasts the widely studied genetically based approaches utilized by bacteria through which bacteria gain resistance to antibiotics as the result of mutations experienced throughout time. This mutation-free response, however, demonstrates that some bacteria need not mutate to survive external stressors, Wood says.
Instead, when triggered by an external stressor such as an antibiotic, a bacterial cell can render itself dormant by triggering an internal reaction that degrades the effectiveness of its own internal antitoxins, Wood explains. With its antitoxins damaged, the toxins present within the bacterial cell are left unchecked and damage the cell's metabolic processes so that it essentially shuts down, he adds.
It's self-inflicted damage but with a purpose.
"The cell normally doesn't want to hurt itself; it wants to grow as fast as possible," Wood states; the raison d'être for a cell is to make another cell," Wood says. "However, most bacteria have this group of proteins, and if this group was active - if you got rid of the antitoxins - this group of toxins would either kill the cell or damage it."
Specifically, Wood and his colleagues found that when encountering oxidative stress, their bacterial cells initiated a process through which an antitoxin called MqsA was degraded, in turn allowing the toxin MqsR to degrade all of the cells' messenger RNA. This messenger RNA, Wood explains, plays a critical intermediate role in the cell's process of manufacturing proteins, so without it the cell can't make proteins. With the protein-manufacturing factory shut down, the bacterial cell goes dormant, and an antibiotic cannot "lock on" to the cell. When the stressor is removed, the bacterial cells eventually come back online and resume their normal activities, Wood says.
"It was the combination of the genetic studies at Texas A&M with our structural studies at Brown University that demonstrated that the proteins MqsR:MqsA form an entirely new family of toxin:antitoxin systems," Page says. "Remarkably, we have shown this system not only controls its own genes, but also many other genes in E. coli, including the gene that controls the response to oxidative stress."
This response mechanism, Wood emphasizes, does not replace the mutation-based approaches that have for years characterized cell behavior; it's merely another method in a multifaceted approach undertaken by bacteria to ensure survival.
"A small community of bacteria is in a sense hedging its bet against a threat to its survival by taking another approach," Wood says. "To the bacteria, this is always a numbers game. In one milliliter you can have a trillion bacterial cells, and they don't always do the same thing under stress.
"If we can determine that this 'going to sleep' is the dominant mechanism utilized by bacteria, then we can begin to figure out how to 'wake them up' so that they will be more susceptible to the antibiotic. This ideally would include simultaneously applying the antibiotic and a chemical that wakes up the bacteria. That's the goal - a more effective antibiotic."
Ryan Garcia | EurekAlert!
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy