Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Research shows why 1 bacterial infection is so deadly in cystic fibrosis patients

23.04.2012
Pathogen interferes with important survival process in cells whose job is to fight infection

Scientists have found why a certain type of bacteria, harmless in healthy people, is so deadly to patients with cystic fibrosis.

The bacterium, Burkholderia cenocepacia, causes a severe and persistent lung infection in patients with CF and is resistant to nearly all known antibiotics. Cystic fibrosis is a chronic disorder characterized by a buildup of mucus in the lungs and other parts of the body, and various types of lung infection are responsible for about 85 percent of deaths in these patients.

The Ohio State University researchers have determined that B. cenocepacia bacteria interfere with an important survival process in cells whose job is to fight infection. This phenomenon is even stronger in CF patients, so the infection exacerbates the cell malfunction.

The research group also showed that rapamycin, an existing drug known to stimulate this cell-survival process, called autophagy, helped control B. cenocepacia infection in mice that serve as a model for cystic fibrosis.

The scientists also dissected the role of a molecule called p62, which plays a role in the autophagy process. They found that p62 inside macrophages, the cells that fight infection, is influential in controlling B. cenocepacia infection.

"This suggests that manipulating p62 levels might help patients with CF fight off the lethal infection," said Amal Amer, assistant professor of microbial infection and immunity and internal medicine at Ohio State and senior author of the study.

The research will be presented April 22 at the American Society for Biochemistry and Molecular Biology annual meeting, which is being held in conjunction with the Experimental Biology 2012 conference in San Diego. The rapamycin findings also were published in a recent issue of the journal Autophagy.

The B. cenocepacia infection remains relatively rare but highly transmissible in patients with cystic fibrosis. "It's really a death sentence for the patient. The disease either progresses with propagation of inflammation and chronic destruction of lung tissue, or acute infection with severe sepsis that occurs very quickly. We don't know which patient will take which course," said Amer, also an investigator in Ohio State's Center for Microbial Interface Biology.

Amer and her colleagues had been studying autophagy in other organisms before experimenting with these bacterial cells. Autophagy allows a cell to digest parts of itself to produce energy when it is experiencing starvation.

"We were among the first to show that autophagy can actually clear infection," Amer said. "So not only is it a physiological pathway in the background all the time, but some bacteria, when they infect cells, will be engulfed by autophagy. And that helps in clearing the infection."

These cells that can use autophagy to clear infection are the macrophages, which are first-responders in the immune system that essentially eat offending pathogens.

Amer and Ohio State doctoral student Basant Abdulrahman showed that macrophages isolated from both mice and humans that carried the most common CF mutation could not clear the B. cenocepacia infection. The bacterium invades the macrophage and just sits there, Amer explained, instead of being digested and cleared away.

Because autophagy was not working in these cells, the researchers tested the effects of the drug rapamycin, an immune-system suppressant that is known to stimulate autophagy, in normal animals and those with the most common CF genetic mutation.

The drug had no real effect on normal mice because they could clear a B. cenocepacia infection on their own, said Abdulrahman, the study's lead author and presenter of the research at Experimental Biology 2012. But in mice with CF, she said, the drug's stimulation of the autophagy process helped these mice clear the bacterial infection from their lungs.

With this strong suggestion that autophagy is a potential target for new CF treatments, the researchers set out to better understand this process in CF macrophages that are unable to fight the B. cenocepacia infection. And that is when they found that p62 shows promise as an even more specific drug target. Additional studies of p62's effects on this bacterial infection are in progress.

This research is supported by grants from the National Institutes of Health and the American Lung Association.

Additional co-authors are Arwa Abu Khweek, Anwari Akhter, Kyle Caution and Mia Tazi of Ohio State's College of Medicine and Benjamin Kopp of Nationwide Children's Hospital.

Contact: Amal Amer, who will be reachable at Ohio State, (614) 247-1566, amal.amer@osumc.edu, or Basant Abdulrahman, abdulrahman.12@osu.edu, who will attend Experimental Biology 2012 and can be reached via email or by calling Emily Caldwell at (614) 292-8310 or Angela Hopp at (713) 471-4541.

Editor's note: The poster (Abstract No. 4186, Program No. 543.4, Poster Board No. A61) will be presented from 1:05 p.m.-2:35 p.m. (PT) Sunday, April 22, in the exhibit hall at Experimental Biology 2012.

About Experimental Biology 2012

Experimental Biology is an annual gathering of six scientific societies that this year is expected to draw 14,000-plus independent scientists and exhibitors. The American Association of Anatomists (AAA) is a co-sponsor of the meeting, along with the American Physiological Society (APS), American Society for Biochemistry and Molecular Biology (ASBMB), American Society for Investigative Pathology (ASIP), American Society for Nutrition (ASN) and the American Society for Pharmacology and Experimental Therapeutics (ASPET).

More information about EB2012 for the media can be found on the press page: http://experimentalbiology.org/EB/pages/Press-Registration.aspx.

About the American Society for Biochemistry and Molecular Biology

The ASBMB is a nonprofit scientific and educational organization with more than 12,000 members worldwide. Most members teach and conduct research at colleges and universities. Others conduct research in various government laboratories, at nonprofit research institutions and in industry. The Society's student members attend undergraduate or graduate institutions. For more information about ASBMB, visit www.asbmb.org.

Angela Hopp | EurekAlert!
Further information:
http://www.asbmb.org

More articles from Life Sciences:

nachricht Algae-killing viruses spur nutrient recycling in oceans
18.07.2019 | Rutgers University

nachricht How are pollen distributed in the air?
18.07.2019 | Leibniz-Institut für Troposphärenforschung e. V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: First-ever visualizations of electrical gating effects on electronic structure

Scientists have visualised the electronic structure in a microelectronic device for the first time, opening up opportunities for finely-tuned high performance electronic devices.

Physicists from the University of Warwick and the University of Washington have developed a technique to measure the energy and momentum of electrons in...

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

Im Focus: Extremely hard yet metallically conductive: Bayreuth researchers develop novel material with high-tech prospects

An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".

The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...

Im Focus: Modelling leads to the optimum size for platinum fuel cell catalysts: Activity of fuel cell catalysts doubled

An interdisciplinary research team at the Technical University of Munich (TUM) has built platinum nanoparticles for catalysis in fuel cells: The new size-optimized catalysts are twice as good as the best process commercially available today.

Fuel cells may well replace batteries as the power source for electric cars. They consume hydrogen, a gas which could be produced for example using surplus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Genetic differences between strains of Epstein-Barr virus can alter its activity

18.07.2019 | Health and Medicine

Algae-killing viruses spur nutrient recycling in oceans

18.07.2019 | Life Sciences

Machine learning platform guides pancreatic cyst management in patients

18.07.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>