Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A wolf in sheep’s clothing: plague bacteria reveal one of their virulence tricks

21.09.2006
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.

... more about:
»Prehna »Yersinia »YpkA »virulence »wild-type

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 Yersinia. 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.”

Kristine Kelly | EurekAlert!
Further information:
http://www.rockefeller.edu

Further reports about: Prehna Yersinia YpkA virulence wild-type

More articles from Life Sciences:

nachricht Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover

nachricht First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Color effects from transparent 3D-printed nanostructures

New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference

Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...

Im Focus: Unraveling the nature of 'whistlers' from space in the lab

A new study sheds light on how ultralow frequency radio waves and plasmas interact

Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...

Im Focus: New interactive machine learning tool makes car designs more aerodynamic

Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.

When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...

Im Focus: Robots as 'pump attendants': TU Graz develops robot-controlled rapid charging system for e-vehicles

Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.

Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....

Im Focus: The “TRiC” to folding actin

Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.

Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

LaserForum 2018 deals with 3D production of components

17.08.2018 | Event News

Within reach of the Universe

08.08.2018 | Event News

A journey through the history of microscopy – new exhibition opens at the MDC

27.07.2018 | Event News

 
Latest News

Smallest transistor worldwide switches current with a single atom in solid electrolyte

17.08.2018 | Physics and Astronomy

Robots as Tools and Partners in Rehabilitation

17.08.2018 | Information Technology

Climate Impact Research in Hannover: Small Plants against Large Waves

17.08.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>