Featured Research

from universities, journals, and other organizations

Bubonic Plague Kills By Cutting Off Cellular Communication

Date:
September 17, 1999
Source:
University Of Michigan
Summary:
Yersinia pestis, the deadly bacterium that causes bubonic plague, kills by cutting off a cell's ability to communicate with other immune system cells needed to fight off the bacterial invasion. University of Michigan scientists identify one protein responsible for the plague's lethal effect and the molecular family it targets.

One molecule holds the key to plague's lethal effects.

Related Articles


Contact: Sally Pobojewski
Phone: (734) 647-1844
E-mail: [email protected]

ANN ARBOR --- Yersinia pestis, the deadly bacterium that causes bubonic plague, kills by cutting off a cell's ability to communicate with other immune system cells needed to fight off the bacterial invasion. In a study published in the Sept. 17 issue of Science, University of Michigan scientists identify one protein responsible for the plague's lethal effect and the molecular family it targets.

"Yersinia is a clever pathogen," says Kim Orth, Ph.D., a research investigator in the U-M Medical School. "It found our Achilles heel --- one family of molecules used by every mammalian cell to transmit signals involved in the immune response and cell death."

If scientists can understand the mechanism Yersinia uses to control cell signaling and how it destroys the immune communications system, it could have important implications in medicine, especially in cancer and immune-related diseases, Orth adds.

"YopJ, the protein Yersinia uses to block this signaling process, is one of six proteins injected by the bacteria into immune cells called macrophages," says Jack E. Dixon, the Minor J. Coon Professor of Biological Chemistry in the U-M Medical School, who directed the research. Every Yop has a specific function and they work together to gain entry into a cell and destroy the body's defense systems.

"In this study, we found that YopJ binds to similar molecules located at the same point in two critical cellular signaling pathways," Dixon says.

The first pathway, called MAPK, controls cell growth and regulates the immune inflammatory response. The second pathway, known as NF(B, also regulates the immune inflammatory response, as well as preventing cell death and controlling embryonic development.

"Scientists thought these two pathways were unrelated, but YopJ recognized a common component in molecules at the mid-point of the MAPK and NF(B pathways," Orth says. "By binding to this one molecule, called MKK in one pathway and IKKbeta in the other, YopJ cuts the main cellular communications cable and shuts down signaling."

Once scientists understand exactly how YopJ binds to and disables MKK and IKKbeta, it should be possible to identify the docking site on this entire superfamily of molecules, which would be an important target for future drug design.

U-M scientists used a yeast two-hybrid screen to determine that YopJ targets all members of the MKK family in mammalian cells, but not other proteins in the MAPK pathway. Additional experiments revealed that the targeted molecule in the NF(B pathway was IKKbeta. Later experiments with mouse macrophages infected with Yersinia showed that YopJ prevented other kinases from activating MKK.

"Because YopJ is found in many species of bacteria --- including Salmonella, an intestinal pathogen, and Rhizobium, symbiotic bacteria involved in nitrogen fixation, it is particularly intriguing," Dixon says. "It is rare that a protein effector is found in both plant and animal pathogens.

"YopJ's molecular structure is slightly different in other bacterial species and it attacks different types of cells, but all YopJ proteins undoubtedly recognize the same molecule in the MAPK pathway," Dixon says. "This indicates YopJ is an important and effective virulence factor, which has been conserved for long periods of evolutionary history."

The study was funded by the National Institutes of Health and the Walther Cancer Institute. Collaborators on the study from the U-M Medical School included Zhao Qin Bao, U-M research associate; Scott Stewart, a U-M graduate student and Amy E. Rudolph, Ph.D., a U-M post-doctoral research fellow. Additional collaborators were James B. Bliska, Ph.D., and graduate student Lance E. Palmer from the State University of New York at Stony Brook.


Story Source:

The above story is based on materials provided by University Of Michigan. Note: Materials may be edited for content and length.


Cite This Page:

University Of Michigan. "Bubonic Plague Kills By Cutting Off Cellular Communication." ScienceDaily. ScienceDaily, 17 September 1999. <www.sciencedaily.com/releases/1999/09/990916134550.htm>.
University Of Michigan. (1999, September 17). Bubonic Plague Kills By Cutting Off Cellular Communication. ScienceDaily. Retrieved November 22, 2014 from www.sciencedaily.com/releases/1999/09/990916134550.htm
University Of Michigan. "Bubonic Plague Kills By Cutting Off Cellular Communication." ScienceDaily. www.sciencedaily.com/releases/1999/09/990916134550.htm (accessed November 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Saturday, November 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

WFP: Ebola Risks Heightened Among Women Throughout Africa

WFP: Ebola Risks Heightened Among Women Throughout Africa

AFP (Nov. 21, 2014) Having children has always been a frightening prospect in Sierra Leone, the world's most dangerous place to give birth, but Ebola has presented an alarming new threat for expectant mothers. Duration: 00:37 Video provided by AFP
Powered by NewsLook.com
Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com
Ebola: Life Without School in Guinea

Ebola: Life Without School in Guinea

AFP (Nov. 21, 2014) Following the closure of schools and universities in Guinea because of the Ebola virus, students look for temporary work or gather in makeshift classrooms to catch up on their syllabus. Duration: 02:14 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins