The work, published in the Proceedings of the National Academy of Sciences, reveals the mechanistic basis for how the MRSA bacterium became such a difficult pathogen over the previous 50 years, in which time it spread rapidly across the world.
Modern strains of MRSA have become broadly resistant to antibiotics, including beta-lactam antibiotics, such as penicillins. In their report, the researchers disclose the discovery of an allosteric domain in the X-ray structure of the penicillin binding protein 2a of MRSA, the enzyme that carries out the crosslinking reaction. (An allosteric site is a place on the protein where its activity is regulated by the binding of another molecule.)
Mobashery, Chang and Juan Hermoso at CSIC, the Spanish Research Council, document that an allosteric trigger by a fragment of the cell wall at a distance of 60 Ångstroms (6 nanometers) activates a set of conformational changes that culminates in the opening of the active site from a closed conformation, enabling catalysis for the physiological role of the enzyme.
They also document that the new beta-lactam antibiotic ceftaroline, recently approved by the Food and Drug Administration, is able to bind to the allosteric domain and trigger the same allosteric opening of the active site. This subversion of the allosteric control allows another molecule of ceftaroline to access the active site, which inhibits the function of the enzyme, leading to cell death by MRSA. This mechanism of action for the antibiotic is unprecedented and offers important insights for design of future drugs to combat MRSA.
MRSA has been a difficult hospital pathogen to control and has emerged in the broader community in the past several years, especially in such places as prisons, locker rooms and nurseries. In the United States alone, the disease infects about 100,000 people and claims the lives of nearly 20,000 people annually.
The paper, titled "How allosteric control of Staphylococcus aureus penicillin binding protein 2a enables methicillin resistance and physiological function," is available online.
Shahriar Mobashery | EurekAlert!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences