Navigation Links
Pathogen turns protein into a virulence factor in 1 easy step
Date:5/6/2013

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.


'/>"/>

Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology
Source:Eurekalert

Related biology news :

1. Researchers uncover molecular pathway through which common yeast becomes fungal pathogen
2. Bees self-medicate when infected with some pathogens
3. College students work to sterilize air, kill pathogens on buses
4. Antitoxin strategy may help target other pathogens
5. Preserved frogs hold clues to deadly pathogen
6. A deeper look into the pathogen responsible for crown gall disease in plants
7. Differences in the genomes of related plant pathogens
8. New key element discovered in pathogenesis of Burkitt lymphoma
9. Compounds shown to thwart stubborn pathogens social propensity
10. Antibiotic residues in sausage meat may promote pathogen survival
11. Antibiotic-resistant pathogens persist in antibiotic-free pigs
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/2/2017)... Summary This report provides all ... and its partnering interests and activities since 2010. ... The Partnering Deals and Alliance since 2010 report provides ... of the world,s leading life sciences companies. ... ensure inclusion of the most up to date deal ...
(Date:2/28/2017)... , Feb. 28, 2017   Acuant , ... software globally, announces significant enhancements to new and core ... 2016. New products include mobile and desktop Acuant FRM ... TM - a real time manual review of ... idScanĀ® technology provides the fastest and most accurate capture ...
(Date:2/26/2017)... Feb. 25, 2017  Securus Technologies, a leading ... for public safety, investigation, corrections and monitoring, announces ... Reentry. "Too often, too many offenders ... county jails are trying to tackle this ongoing ... friends and family members. While significant steps are underway, ...
Breaking Biology News(10 mins):
(Date:3/28/2017)... -RepliCel Life Sciences Inc. (OTCQB: REPCF) (TSXV: RP) (FRA:P6P2) ("RepliCel" ... clinical data from its phase 1/2 tendon repair study investigating ... (RCT-01) as a treatment for Achilles tendinosis. ... The clinical trial ... 6 months and showed no serious adverse events related to ...
(Date:3/27/2017)... Properties (NYSE: CUZ ) announced today that Amgen, ... 10-year, approximately 125,000 square-foot lease at Corporate Center, a 1,224,000 ... submarket of Tampa, FL. ... for their new location in Tampa ," ... of Cousins Properties. "Amgen is a cutting-edge global company at ...
(Date:3/27/2017)... The new research portal will give ... reports on Valero Energy , offering extensive market research ... ... (Logo: http://photos.prnewswire.com/prnh/20160330/349511LOGO) The latest trend gaining ... Ethanol today, even though touted as a green alternative to ...
(Date:3/27/2017)... , March 27, 2017 Neurotrope, ... novel therapies for neurodegenerative diseases, including Alzheimer,s disease, ... its application to list the Company,s common stock ... by The NASDAQ Stock Market, a unit of ... listing, Neurotrope will ring the Opening Bell at the ...
Breaking Biology Technology: