In a study to be published May 7 in mBio®, the online open-access journal of the American Society for Microbiology, scientists at Emory University School of Medicine, the University of Virginia, and Universidad de las Islas Baleares in Mallorca, Spain, uncover this previously unknown virulence factor in P. aeruginosa, one of the most common causes of hospital-acquired pneumonia.
Co-author Joanna Goldberg of Emory says scientists have long thought P. aeruginosa mostly uses this protein called elongation factor-Tu (EF-Tu) inside the cell, but she and her collaborators have learned that as a virulence factor, it could represent a vulnerability for the bacterium. "EF-Tu is presumed to be an essential protein, and it's performing these moonlighting functions as well. If we figured out how it was doing that, we could devise strategies to inhibit it," says Goldberg.
P. aeruginosa pneumonia is a big problem in the hospital setting, where it is a frequent cause of hospital-acquired pneumonia and is the leading cause of death among critically ill patients whose airways have been damaged by ventilation, trauma, or other infections. The pathogen is also a contributor to disease in the lungs of cystic fibrosis patients and forms thick biofilms that are difficult or impossible to treat with antibiotics. Goldberg and her co-author Sebastian Alberti and their colleagues study the molecular events that enable the bacterium to infect human cells in the hopes of finding ways to prevent P. aeruginosa pneumonia.
In their earlier work, Goldberg and Alberti found that P. aeruginosa takes the protein EF-Tu, which was generally thought to exist only inside the cell, and decorates the exterior of the cell with it, but in a modified form. This modified EF-Tu is recognized by antibodies to the common bacterial epitope phosphorylcholine (ChoP), indicating that the EF-Tu is modified somehow to mimic ChoP, allowing P. aeruginosa to enjoy the benefits of ChoP. By interacting with receptors on human cells, ChoP carries out a crucial step for setting up an infection for a number of different types of respiratory pathogens.
But how is EF-Tu modified, they wondered? And does it help P. aeruginosa establish an infection? This study answers those questions.
Using a host of techniques, including mass spectrometry, site directed mutagenesis of key residues in the protein, and genetic loss of function/gain of function studies, they found that P. aeruginosa only makes small changes to EF-Tu to get it to mimic this powerful ligand. P. aeruginosa transfers three methyl groups to a lysine on EF-Tu, giving it a structure similar to ChoP and allowing it to fit in the PAFR receptor in the way ChoP does.
But the modified EF-Tu not only looks like ChoP, in many ways it works like ChoP: testing in cultures of human airway cells shows that the modification of EF-Tu enables the bacterium to adhere to human cells.
"It allows [P. aeruginosa] to adhere to the cells and invade," says Goldberg. "And it seems to be involved in virulence in mouse models. It might also impact persistence in the lung."
As an environmental pathogen, P. aeruginosa lives in soil, water, and other environments outside the body, a fact that may offer a clue why it uses this re-purposed protein as a virulence factor. Proteins that can be put to work in both worlds - in the environment and the in the human host - would be useful to P. aeruginosa in much the way a spork can allow you to enjoy both the coleslaw and the pudding in your take out dinner.
"Its interaction with humans is accidental. It's an opportunist. The fact that it has this novel modification on this protein that is inherent in the bacterium that enables it to attach and persist and cause disease is exciting," says Goldberg.
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://mbio.asm.org.
The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM's mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.
Jim Sliwa | EurekAlert!
Colorectal cancer risk factors decrypted
13.07.2018 | Max-Planck-Institut für Stoffwechselforschung
Algae Have Land Genes
13.07.2018 | Julius-Maximilians-Universität Würzburg
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....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
13.07.2018 | Event News
13.07.2018 | Materials Sciences
13.07.2018 | Life Sciences