Navigation Links
A wolf in sheep's clothing: Plague bacteria reveal one of their virulence tricks

The bacterium that causes the plague belongs to a virulent family of bacteria called Yersinia, a group that also includes a pathogen responsible for food poisoning. These bacteria insert into their host cells proteins and other virulence factors, which kill by -- among other things -- disrupting the cells' normal structure. One of these proteins, called YpkA, attacks a cell's internal skeleton. Now, a study published by Rockefeller University researchers in the most recent issue of Cell shows exactly how YpkA does this, proving the protein's mechanism from the atomic to the organismal level and providing a potential target for new antibiotic drugs.

C. Erec Stebbins, associate professor and head of the Laboratory of Structural Microbiology, and graduate student Gerd Prehna solved the structure for one region of the YpkA protein, a "binding domain" where it interlocks with another protein on the host cell's membrane. By looking at the crystal structure of this protein-protein complex, Prehna discovered that the configuration looked just like one formed by some of the host's own signaling proteins. And it's this mimicry, he found, that leads to a signaling shutdown and deregulation of the cell's normal structure.

After establishing this effect, Prehna set about disrupting it by mutation. Using the structure to guide him, he changed three amino acids of YpkA that contacted host proteins, and then looked at how the mutated bacteria affected human cells compared to the original wild-type Yersinia. His results confirmed the hypothesis from the structural study: While the wild-type YpkA wreaked havoc on their host cells' cytoskeletons, the mutant left the actin-based skeleton intact.

Then, the researchers took it one step further. Stebbins and Prehna worked with collaborators at Stony Brook University, who created Yersinia bacteria with Prehna's mutations. The Stony Brook researchers then injected mice with the wild-type and mutant strains of Yersini a. All the mice infected with the wild-type bacteria died within nine days of exposure. But the group that received the YpkA mutant had an 80 percent survival rate, showing that Prehna's mutation drastically lowered Yersinia's harmful effects. "Altering this binding site not only impairs the bacteria's ability to disrupt the host cytoskeleton," Stebbins says, "but it decreases its virulence significantly."

"It's rare to find something that has such a strong effect that you can hit one protein so specifically, knock out essentially half its activity, and have such a dramatic result," he says. "Not only did we have a mechanistic explanation, but we could connect what we were seeing in animal studies all the way down to what was happening at the atomic level."


'"/>

Source:Rockefeller University


Related biology news :

1. Plague proteome reveals proteins linked to infection
2. Anti-bacterial additive widespread in U.S. waterways
3. A bacterial genome reveals new targets to combat infectious disease
4. Discovery of key proteins shape could lead to improved bacterial pneumonia vaccine
5. Scientists discover that host cell lipids facilitate bacterial movement
6. Family trees of ancient bacteria reveal evolutionary moves
7. Drug-resistant bacteria on poultry products differ by brand
8. Programmable cells: Engineer turns bacteria into living computers
9. NASA links nanobacteria to kidney stones and other diseases
10. Substance protects resilient staph bacteria
11. Physiological effects of reduced gravity on bacteria
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:11/29/2016)... , Nov. 29, 2016 BioDirection, a ... point-of-care products for the objective detection of concussion and ... company has successfully completed a meeting with the U.S. ... Tbit™ blood test Pre-Submission Package. During the meeting company ... system as a precursor to commencement of a planned ...
(Date:11/24/2016)... Nov. 23, 2016 Cercacor today introduced Ember ... their trainers non-invasively measure hemoglobin, Oxygen Content, ... and Respiration Rate in approximately 30 seconds. Smaller than ... and immediate access to key data about their bodies ... training regimen. Hemoglobin carries oxygen to ...
(Date:11/19/2016)... , Nov. 18, 2016 Securus Technologies, a ... for public safety, investigation, corrections and monitoring, announced today ... competitor, ICSolutions, to have an independent technology judge determine ... most modern high tech/sophisticated telephone calling platform, and the ... that they do most of what we do – ...
Breaking Biology News(10 mins):
(Date:11/30/2016)... ... November 30, 2016 , ... SSCI, the established leader in small-molecule cocrystal technology ... latest FDA guidance on pharmaceutical cocrystals as drug substance . The Lunch ... , The event follows the successful November 15th event that took place in Burlingame, ...
(Date:11/30/2016)... (PRWEB) , ... November 30, 2016 , ... ... in the development of a new orally administered treatment for Alzheimer’s disease (AD), ... results of a Phase 2a clinical trial of T3D-959 in mild to moderate ...
(Date:11/30/2016)... London, UK (PRWEB) , ... November 30, 2016 , ... ... old offices on Haymarket after five years and look forward to continuing their expansion ... heart of Soho, an area which has been traditionally favoured by the creative industries, ...
(Date:11/30/2016)... ... November 30, 2016 , ... Microbial ... venture founded by Arianna Huffington, as part of the Thrive Global pop-up store. ... Kit, enabling purchasers to explore the microorganisms in their gut, collectively known as ...
Breaking Biology Technology: