Featured Research

from universities, journals, and other organizations

New Theory Proposed For Cystic Fibrosis Infections

Date:
November 20, 2001
Source:
NIH/National Institute Of Allergy And Infectious Diseases
Summary:
Cystic fibrosis (CF) is a fatal lung disease caused by an altered gene, but how the gene affects cells is not completely understood. Now, researchers have new evidence suggesting the gene can change the internal chemistry of some lung cells, making them more susceptible to certain bacteria that cause sickness and, ultimately, death. The investigators also used a simple process to correct those changes in the test tube.

Cystic fibrosis (CF) is a fatal lung disease caused by an altered gene, but how the gene affects cells is not completely understood. Now, researchers have new evidence suggesting the gene can change the internal chemistry of some lung cells, making them more susceptible to certain bacteria that cause sickness and, ultimately, death. The investigators also used a simple process to correct those changes in the test tube. The study appears in the Proceedings of the National Academy of Sciences online early edition.

"This research proposes a novel explanation for why lung infections are so persistent in cystic fibrosis," says Christopher Taylor, Sc.D., an expert on bacterial respiratory diseases with the National Institute of Allergy and Infectious Diseases (NIAID), which funded the study. "If additional studies support the findings presented here, we will have a better understanding of the disease and perhaps new ways to treat it."

People with CF battle chronic respiratory infections and have difficulty breathing because of mucus accumulation in the lungs. Most patients ultimately die from a buildup of Pseudomonas aeruginosa, a common bacterium that rarely causes disease in healthy individuals.

Although the CF gene has been known since 1989, exactly how it is linked to increased susceptibility to P. aeruginosa and other bacteria is unknown. The gene encodes a protein called CFTR, which regulates the flow of charged atoms, or ions, into and out of cells. Maintaining a proper ion balance is critical for cells to function properly, but researchers have not known how an imbalance makes the lung cells a more attractive site for bacteria to grow.

To solve that riddle, Jens Poschet, Ph.D., and Vojo Deretic, Ph.D., began to study the link between CFTR and bacterial infections while both researchers were at the University of Michigan; they are now at the University of New Mexico. Because bacteria must adhere to proteins on the cell surface before they can invade, the researchers wondered if a malfunctioning CFTR could lead to changes in those surface proteins. If so, perhaps the cell surface would become more amenable to invading bacteria.

Drs. Deretic and Poschet first looked inside cells, where all proteins are made and then transported to a series of internal compartments for final processing. Some of those compartments form the trans-Golgi network, a type of central packaging center that sorts proteins and gives them their finishing touches. Among those touches, specific enzymes attach small sugar molecules to many surface proteins. The sugars serve as molecular flags that help the proteins recognize other cells or chemical signals.

When the researchers studied the trans-Golgi network in cells with an altered CFTR, they found the compartments were more acidic than normal and failed to attach the appropriate sugar molecules to the proteins bound for the cell surface. "The sugar-adding enzymes only work in a specific pH range. The altered CFTR appears to throw off the ion balance in the cells, messing up the pH," explains Dr. Deretic.

Without the sugars on the cell surface, P. aeruginosa and other bacteria stuck to the cells much more readily, suggesting a clear link between the CFTR gene and increased susceptibility to respiratory infections. When the investigators treated the cells in a test tube by restoring normal acidity, the bacteria no longer could adhere. "This was an exciting discovery to us, because in the test tube at least we can correct the deficiency with simple maneuvers," says Dr. Deretic.

If their findings hold true in people as well, Dr. Deretic sees the potential for a new approach to treatment. "We already have ion pump inhibitors and antacids for treating heartburn," he says. "If we can design similar compounds to go to the lungs, we might have a simple solution to greatly improve the health of CF patients."

###NIAID is a component of the National Institutes of Health (NIH). NIAID supports basic and applied research to prevent, diagnose, and treat infectious and immune-mediated illnesses, including HIV/AIDS and other sexually transmitted diseases, tuberculosis, malaria, autoimmune disorders, asthma and allergies.

Reference:JF Poschet, et al. Molecular basis for defective glycosylation and Pseudomonas pathogenesis in cystic fibrosis lung. Proceedings of the National Academy of Sciences Early Edition online (November 20, 2001) 10.1073/pnas.241182598.


Story Source:

The above story is based on materials provided by NIH/National Institute Of Allergy And Infectious Diseases. Note: Materials may be edited for content and length.


Cite This Page:

NIH/National Institute Of Allergy And Infectious Diseases. "New Theory Proposed For Cystic Fibrosis Infections." ScienceDaily. ScienceDaily, 20 November 2001. <www.sciencedaily.com/releases/2001/11/011120043413.htm>.
NIH/National Institute Of Allergy And Infectious Diseases. (2001, November 20). New Theory Proposed For Cystic Fibrosis Infections. ScienceDaily. Retrieved August 30, 2014 from www.sciencedaily.com/releases/2001/11/011120043413.htm
NIH/National Institute Of Allergy And Infectious Diseases. "New Theory Proposed For Cystic Fibrosis Infections." ScienceDaily. www.sciencedaily.com/releases/2001/11/011120043413.htm (accessed August 30, 2014).

Share This




More Health & Medicine News

Saturday, August 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

3 Things To Know About The Ebola Outbreak's Progression

3 Things To Know About The Ebola Outbreak's Progression

Newsy (Aug. 29, 2014) Here are three things you need to know about the deadly Ebola outbreak's progression this week. Video provided by Newsy
Powered by NewsLook.com
Killer Amoeba Found in Louisiana Water System

Killer Amoeba Found in Louisiana Water System

AP (Aug. 28, 2014) State health officials say testing has confirmed the presence of a killer amoeba in a water system serving three St. John the Baptist Parish towns. (Aug. 28) Video provided by AP
Powered by NewsLook.com
Who Could Be Burnt by WHO's E-Cigs Move?

Who Could Be Burnt by WHO's E-Cigs Move?

Reuters - Business Video Online (Aug. 28, 2014) The World Health Organisation has called for the regulation of electronic cigarettes as both tobacco and medical products. Ciara Lee looks at the impact of the move on the tobacco industry. Video provided by Reuters
Powered by NewsLook.com
CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

CDC Director On Ebola Outbreak: 'It's Worse Than I Feared'

Newsy (Aug. 28, 2014) CDC director Tom Frieden says the Ebola outbreak is even worse than he feared. But he also said there's still hope to contain it. 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