But the Jeff Brinker research group has determined that the very first stage of staph infection, when bacteria switch from a harmless to a virulent form, occurs in a single cell and that this individual process can be stopped by the application of a simple protein.
The Brinker group’s nonantibiotic approach may make it easier to treat staphylococci strains that have become drug resistant like the methicillin-resistant Staphylococcus aureus MRSA. The control of such strains is a formidable problem in hospitals.
“The good news is that by inhibiting the single cell’s signaling molecules with a small protein, we were able to suppress any genetic reprogramming into the bacterium’s more virulent form,” said Brinker. “Our work clearly showed the strategy worked.”
Brinker, with appointments at Sandia National Laboratories and the University of New Mexico, wrote about his group’s findings in the Nov. 22 issue of Nature Chemical Biology.
In the course of its experiments, the Brinker team achieved three firsts:
They isolated Staphylococcus aureus bacteria in individual, self-assembled nanoscale compartments. Isolation of an individual bacterium previously had been achieved only computationally, leaving open questions of how a physically and chemically isolated bacterium would actually behave.
They demonstrated that it was the release of signaling peptides from a single cell — not a quorum — that acted as a trigger to reprogram that same cell so that it released toxins.
By introducing an inexpensive, very low-density lipoprotein (VLDL) to bind to the messenger peptide, they stopped the single cell from reprogramming itself.
The term “quorum sensing” itself may prove a misnomer, the result of observations made in cell cultures rather than in the body, said Brinker. Because signaling molecules tend to diffuse away, a liquid culture of cells would naturally require many bacteria to produce enough signaling bacteria to begin reprogramming. The situation is otherwise in nature, where even a single cell may be sufficiently isolated that its own manufactured peptides would remain in its vicinity.
“Also, it’s hard to believe that one cell’s evolution could be based on what a whole bunch of cells do,” said Brinker. “When we instead consider that an individual cell will do what’s best for it, we can more clearly understand the benefits of that cell’s behavior.”
A bacterium may live longer by reprogramming itself to produce toxins or enzymes that allow it to access external nutrients, the Brinker group showed.
One aspect of experimental rigor was the team’s ability to organize living cells into a nanostructured matrix. “We’ve already done this with yeast,” said Brinker. “We just extended the process to bacteria.”
A key question was whether a cell could distinguish between peptides emitted by itself from those sent by other cells. If signaling peptides were chemically the same, what would it matter which bacterium emitted it?
As it turned out, said Brinker, “Peptides could bond to surface receptors on their own [generating] cell. So a single cell’s peptide molecules could activate its own genes to express proteins that make staph virulent.”
Indicating that the experiment had isolated the actual cause of the transformation, when the number of peptides produced by a cell ultimately came to exceed the number of lippoprotein molecules in solution, a stalled “quorum-sensing” procedure started up again.
When still more signaling molecules were added to the mix, the cell’s transformation occurred more rapidly.
Researchers hope to find a mechanism to locate bacteria reprogramming in the body so that the antidote can be delivered in time. The problem could be solved, suggested Brinker, by the insertion of VLDL-bearing nanospheres (another Brinker-group creation) into the bloodstream, linked to a ‘searcher’ molecule designed to find and link to suspect peptides or cells that produce them.
“Inhibiting this specific signaling molecule from turning on virulence wouldn’t inhibit other bacteria,” Brinker said.
Targeting is important because the human gastro-intestinal system contains many useful bacteria. These are often decimated by conventional antibiotics but would be spared by the Brinker group’s method.
Brinker, a Sandia Fellow and distinguished professor of chemical engineering and molecular genetics and microbiology at UNM, performed this work with Eric Carnes and DeAnna Lopez at the UNM Department of Chemical and Nuclear Engineering (Lopez is now a Sandia technologist), Graham Timmins at the UNM College of Pharmacy, Niles Donegan and Ambrose Cheung at Dartmouth Medical School, and Hattie Gresham at the New Mexico Veterans Administration Health Care System.
The Sandia work is supported by the Basic Energy Sciences / Division of Materials Science and Engineering and Sandia’s Laboratory Directed Research and Development (LDRD) program. Other project work is supported by the Air Force Office of Scientific Research, the National Science Foundation, the Defense Threat Reduction Agency and the National Institutes of Health.
Sandia National Laboratories is a multiprogram laboratory operated by Sandia Corporation, an autonomous Lockheed Martin company, for the U.S. Department of Energy’s National Nuclear Security Administration. With main facilities in Albuquerque, N.M., and Livermore, Calif., Sandia has major R&D responsibilities in national security, energy and environmental technologies, and economic competitiveness.
Neal Singer | Newswise Science News
Researchers identify potentially druggable mutant p53 proteins that promote cancer growth
09.12.2016 | Cold Spring Harbor Laboratory
Plant-based substance boosts eyelash growth
09.12.2016 | Fraunhofer-Institut für Angewandte Polymerforschung IAP
Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.
Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
09.12.2016 | Life Sciences
09.12.2016 | Ecology, The Environment and Conservation
09.12.2016 | Health and Medicine