Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Plague alters cell death to kill host

15.04.2014

Scientists discover how bacteria Y. pestis overwhelms the lungs to cause pneumonic plague

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.

... more about:
»Allergy »Cell »Infectious »Medicine »apoptosis »death »protein »receptor

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.

###

The work was supported by National Institute of Allergy and Infectious Diseases at National Institutes of Health grants T32 AI007476 and R01 AI093727.

Marla Paul | Eurek Alert!
Further information:
http://www.northwestern.edu

Further reports about: Allergy Cell Infectious Medicine apoptosis death protein receptor

More articles from Life Sciences:

nachricht Pathogenic bacteria hitchhiking to North and Baltic Seas?
22.07.2016 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung

nachricht Unconventional quasiparticles predicted in conventional crystals
22.07.2016 | Max-Planck-Institut für Chemische Physik fester Stoffe

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Newly discovered material property may lead to high temp superconductivity

Researchers at the U.S. Department of Energy's (DOE) Ames Laboratory have discovered an unusual property of purple bronze that may point to new ways to achieve high temperature superconductivity.

While studying purple bronze, a molybdenum oxide, researchers discovered an unconventional charge density wave on its surface.

Im Focus: Mapping electromagnetic waveforms

Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.

Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...

Im Focus: Continental tug-of-war - until the rope snaps

Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases

Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...

Im Focus: A Peek into the “Birthing Room” of Ribosomes

Scaffolding and specialised workers help with the delivery – Heidelberg biochemists gain new insights into biogenesis

A type of scaffolding on which specialised workers ply their trade helps in the manufacturing process of the two subunits from which the ribosome – the protein...

Im Focus: New protocol enables analysis of metabolic products from fixed tissues

Scientists at the Helmholtz Zentrum München have developed a new mass spectrometry imaging method which, for the first time, makes it possible to analyze hundreds of metabolites in fixed tissue samples. Their findings, published in the journal Nature Protocols, explain the new access to metabolic information, which will offer previously unexploited potential for tissue-based research and molecular diagnostics.

In biomedical research, working with tissue samples is indispensable because it permits insights into the biological reality of patients, for example, in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

GROWING IN CITIES - Interdisciplinary Perspectives on Urban Gardening

15.07.2016 | Event News

SIGGRAPH2016 Computer Graphics Interactive Techniques, 24-28 July, Anaheim, California

15.07.2016 | Event News

Partner countries of FAIR accelerator meet in Darmstadt and approve developments

11.07.2016 | Event News

 
Latest News

The Exception and its Rules

25.07.2016 | Physics and Astronomy

Using Ultrashort Pulsed Laser Radiation to Process Fibre-Reinforced Components

25.07.2016 | Materials Sciences

Added bacterial film makes new mortar resistant to water uptake

25.07.2016 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>