Featured Research

from universities, journals, and other organizations

Plague alters cell death to kill host

Date:
April 14, 2014
Source:
Northwestern University
Summary:
The bacteria that cause pneumonic plague can subvert apoptotic cell death by directly destroying Fas ligand, and the way it does this has been the focus of new research. The effect is a disrupted immune response during infection, which allows Y. pestis to overwhelm the lungs, causing death. Pneumonic plague is unique in that it is the only type of plague with an ability to spread from person to person. It is treatable if caught early, but after 24 hours, antibiotics are rendered useless.

Northwestern Medicine scientists are continuing to unravel the molecular changes that underlie one of the world's deadliest and most infamous respiratory infections.

When the bacterium Yersinia pestis enters the lungs, it causes pneumonic plague, a disease that is 100 percent fatal if untreated. The way in which Y. pestis evades the immune system and kills people in a matter of days has largely confounded scientists, until now.

Following a 2007 study demonstrating that the presence of a protein called the plasminogen activator protease (Pla) is required for Y. pestis to live inside the lungs, Wyndham Lathem, PhD, assistant professor in Microbiology-Immunology, has found what role Pla plays during disease.

The activator shuts down a molecule, Fas ligand (FasL), which stimulates a form of programmed cell death known as apoptosis. The result is a disrupted immune response during infection. This allows Y. pestis to overwhelm the lungs, causing death.

"This is the first time anyone has shown how bacteria can subvert apoptotic cell death by directly destroying Fas ligand," said Lathem, a member of the Center for Genetic Medicine and Interdepartmental Immunobiology Center.

The findings were published April 9 in Cell Host & Microbe.

To study its effects, scientists added Pla to glass slides with various fluorescently-tagged proteins. If the protease showed an affinity for a specific protein, it would chew off pieces, making it appear less florescent when viewed under a microscope.

"We knew that Pla must be chopping up host proteins in some manner and we looked to discover exactly what proteins were being affected," said first author Adam Caulfield, a research associate in Lathem's lab.

"As we reviewed possible hits, the 'aha moment' came when we saw Fas ligand on the list of affected proteins, because we know Fas is an integral receptor for controlling cell death," said Lathem. "The process of Pla degrading Fas ligand effectively prevents the lungs from being able to clear the infection."

After verifying their findings using cell cultures, Lathem conducted preclinical tests using mice, arriving at the same conclusion.

"Now that we have identified this as a method by which plague bacteria can manipulate the immune system, we have something to look for when studying other respiratory infections," Lathem said. "This could be a common feature, where we see other bacteria manipulating cell death pathways by altering Fas signaling."

Pneumonic plague is unique in that it is the only type of plague with an ability to spread from person to person. It is treatable if caught early, but after 24 hours, antibiotics are rendered useless.

Lathem believes that a restoration of Fas signaling may give antibiotics more time to work, and scientists in his lab are exploring that possibility. They will also be looking at different bacterial infections to see if any manipulate cell death by altering Fas signaling in a similar manner.


Story Source:

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


Journal Reference:

  1. AdamJ. Caulfield, MargaretE. Walker, LindsayM. Gielda, WyndhamW. Lathem. The Pla Protease of Yersinia pestis Degrades Fas Ligand to Manipulate Host Cell Death and Inflammation. Cell Host & Microbe, 2014; 15 (4): 424 DOI: 10.1016/j.chom.2014.03.005

Cite This Page:

Northwestern University. "Plague alters cell death to kill host." ScienceDaily. ScienceDaily, 14 April 2014. <www.sciencedaily.com/releases/2014/04/140414154500.htm>.
Northwestern University. (2014, April 14). Plague alters cell death to kill host. ScienceDaily. Retrieved July 25, 2014 from www.sciencedaily.com/releases/2014/04/140414154500.htm
Northwestern University. "Plague alters cell death to kill host." ScienceDaily. www.sciencedaily.com/releases/2014/04/140414154500.htm (accessed July 25, 2014).

Share This




More Plants & Animals News

Friday, July 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

How to Make Single Serving Smoothies: Howdini Hacks

How to Make Single Serving Smoothies: Howdini Hacks

Howdini (July 24, 2014) Smoothies are a great way to get in lots of healthy ingredients, plus they taste great! Howdini has a trick for making the perfect single-size smoothie that will save you time on cleanup too! All you need is a blender and a mason jar. Video provided by Howdini
Powered by NewsLook.com
Boy Attacked by Shark in Florida

Boy Attacked by Shark in Florida

Reuters - US Online Video (July 24, 2014) An 8-year-old boy is bitten in the leg by a shark while vacationing at a Florida beach. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Goma Cheese Brings Whiff of New Hope to DRC

Goma Cheese Brings Whiff of New Hope to DRC

Reuters - Business Video Online (July 24, 2014) The eastern region of the Democratic Republic of Congo, mainly known for conflict and instability, is an unlikely place for the production of fine cheese. But a farm in the village of Masisi, in North Kivu is slowly transforming perceptions of the area. Known simply as Goma cheese, the Congolese version of Dutch gouda has gained popularity through out the region. Ciara Sutton reports. Video provided by Reuters
Powered by NewsLook.com
Tyrannosaur Pack-Hunting Theory Aided By New Footprints

Tyrannosaur Pack-Hunting Theory Aided By New Footprints

Newsy (July 24, 2014) A new study claims a set of prehistoric T-Rex footprints supports the theory that the giant predators hunted in packs instead of alone. Video provided by Newsy
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:
from the past week

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