Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Pathogen turns protein into a virulence factor in 1 easy step

To infect its host, the respiratory pathogen Pseudomonas aeruginosa takes an ordinary protein usually involved in making other proteins and adds three small molecules to turn it into a key for gaining access to human cells.

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

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!
Further information:

More articles from Life Sciences:

nachricht Gene therapy shows promise for treating Niemann-Pick disease type C1
27.10.2016 | NIH/National Human Genome Research Institute

nachricht 'Neighbor maps' reveal the genome's 3-D shape
27.10.2016 | International School of Advanced Studies (SISSA)

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Etching Microstructures with Lasers

Ultrafast lasers have introduced new possibilities in engraving ultrafine structures, and scientists are now also investigating how to use them to etch microstructures into thin glass. There are possible applications in analytics (lab on a chip) and especially in electronics and the consumer sector, where great interest has been shown.

This new method was born of a surprising phenomenon: irradiating glass in a particular way with an ultrafast laser has the effect of making the glass up to a...

Im Focus: Light-driven atomic rotations excite magnetic waves

Terahertz excitation of selected crystal vibrations leads to an effective magnetic field that drives coherent spin motion

Controlling functional properties by light is one of the grand goals in modern condensed matter physics and materials science. A new study now demonstrates how...

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

How nanoscience will improve our health and lives in the coming years

27.10.2016 | Materials Sciences

OU-led team discovers rare, newborn tri-star system using ALMA

27.10.2016 | Physics and Astronomy

'Neighbor maps' reveal the genome's 3-D shape

27.10.2016 | Life Sciences

More VideoLinks >>>