Featured Research

from universities, journals, and other organizations

Cystic Fibrosis Patients May Breathe Easier, Thanks To Bioengineered Antimicrobials

Date:
September 27, 2007
Source:
University of Illinois at Urbana-Champaign
Summary:
By better understanding how antimicrobials bind and thereby get inactivated in the mucus of air passages, researchers may have found a way to help cystic fibrosis patients fight off deadly infections. Long-term bacterial infections are the primary cause of death in cystic fibrosis.

Illinois researchers Gerard Wong and Erik Luijten (in photo) may have found a way to help cystic fibrosis patients fight deadly infections.
Credit: University of Illinois Photo

By better understanding how antimicrobials bind and thereby get inactivated in the mucus of air passages, researchers at the University of Illinois may have found a way to help cystic fibrosis patients fight off deadly infections.

"While not a cure, this work has potential as a therapeutic strategy against bacterial infections in cystic fibrosis," said Gerard Wong a professor of materials science and engineering, of physics, and of bioengineering at the U. of I., and a corresponding author of a paper accepted for publication in the Proceedings of the National Academy of Sciences.

Ordinarily, pulmonary passages are lined with a thin layer of mucus that traps bacteria and other pathogens. Moved along by the motions of countless cilia, the mucus also acts as a conveyor belt that disposes of the debris. In patients with cystic fibrosis, however, the mucus is more like molasses -- thick and viscous. Because the cilia can no longer move the mucus, the layer becomes stuck, and the bacteria grow, multiply and colonize. Long-term bacterial infections are the primary cause of death in cystic fibrosis.

Using synchrotron X-ray scattering and molecular dynamics simulations, the researchers took a closer look at the mucous mess.

Debris in the infected mucus includes negatively charged, long-chained molecules such as mucin, DNA and actin (from dead white blood cells). It turns out most of the body's antimicrobials, such as lysozyme, are positively charged.

"We found that actin and lysozyme -- two of the most common components in infected mucus -- form ordered bundles of aligned molecules, which is something you don't expect in something as messy as mucus," said Wong, who also is a researcher at the university's Beckman Institute. "Held together tightly by the attraction of opposite charge, these bundles basically lock up the antimicrobials so that they are unable to kill bacteria."

The researchers then developed a computational model to mimic the biological system. "The model accurately predicted the structure of the actin-lysozyme bundles, and agreed quantitatively with the small-angle X-ray scattering experiments," said Erik Luijten, a professor of materials science and engineering, and of physics, as well as a researcher at the Beckman Institute and the other corresponding author of the PNAS paper.

The next step was to find a way to liberate the lysozyme, or prevent it from binding in the first place. Using their model, the researchers explored the consequences of varying the positive charge on the lysozyme.

"When we reduced the charge, we found a huge effect in our model," Luijten said. "The lysozyme would not bind to the actin. It floated around independently in the mucus."

Then, through genetic engineering, the researchers made lysozyme with roughly half the normal charge. Experiments confirmed the simulations; the reduced charge prevented lysozyme from sticking to actin, without significantly reducing the all-important antimicrobial activity.

Although much work remains, future cystic fibrosis patients might use an inhaler to deliver genetically modified charge-reduced antimicrobials to upper airways. There, these 'non-stick' antimicrobials would go to work killing bacteria, and mitigate against long-term infection.

The implications of this research extend into other areas as well. In water purification, for example, one of the steps involves putting positively charged molecules in the water to grab negatively charged pollutants. The resulting aggregates settle to the bottom of holding tanks and are removed from the water supply.

"A better understanding of how oppositely charged molecules bind in aqueous environments could lead to ways of removing emerging pathogens in water purification," Wong said.

Besides Wong and Luijten, co-authors of the paper are postdoctoral research associate and lead author Lori Sanders, lecturer Wujing Xian, graduate student Camilo Guαqueta, and undergraduate students Michael Strohman and Chuck Vrasich.  The paper is to be posted the week of September 24 on the PNAS website.

Funding was provided by the National Institutes of Health, the Cystic Fibrosis Foundation, the National Science Foundation and the U. of I. WaterCAMPWS Science and Technology Center. Portions of the work were carried out at the Stanford Synchrotron Radiation Laboratory and at the Advanced Photon Source.


Story Source:

The above story is based on materials provided by University of Illinois at Urbana-Champaign. Note: Materials may be edited for content and length.


Cite This Page:

University of Illinois at Urbana-Champaign. "Cystic Fibrosis Patients May Breathe Easier, Thanks To Bioengineered Antimicrobials." ScienceDaily. ScienceDaily, 27 September 2007. <www.sciencedaily.com/releases/2007/09/070925090256.htm>.
University of Illinois at Urbana-Champaign. (2007, September 27). Cystic Fibrosis Patients May Breathe Easier, Thanks To Bioengineered Antimicrobials. ScienceDaily. Retrieved September 18, 2014 from www.sciencedaily.com/releases/2007/09/070925090256.htm
University of Illinois at Urbana-Champaign. "Cystic Fibrosis Patients May Breathe Easier, Thanks To Bioengineered Antimicrobials." ScienceDaily. www.sciencedaily.com/releases/2007/09/070925090256.htm (accessed September 18, 2014).

Share This



More Health & Medicine News

Thursday, September 18, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Artificial Sweetener Could Promote Diabetes

Artificial Sweetener Could Promote Diabetes

Newsy (Sep. 17, 2014) — Doctors once thought artificial sweeteners lacked the health risks of sugar, but a new study says they can impact blood sugar levels the same way. Video provided by Newsy
Powered by NewsLook.com
Ebola Vaccine Trial Gets Underway at Oxford University

Ebola Vaccine Trial Gets Underway at Oxford University

AFP (Sep. 17, 2014) — A healthy British volunteer is to become the first person to receive a new vaccine for the Ebola virus after US President Barack Obama called for action against the epidemic and warned it was "spiralling out of control." Duration: 01:02 Video provided by AFP
Powered by NewsLook.com
Obesity Rates Steady Even As Americans' Waistlines Expand

Obesity Rates Steady Even As Americans' Waistlines Expand

Newsy (Sep. 17, 2014) — Researchers are puzzled as to why obesity rates remain relatively stable as average waistlines continue to expand. Video provided by Newsy
Powered by NewsLook.com
President To Send 3,000 Military Personnel To Fight Ebola

President To Send 3,000 Military Personnel To Fight Ebola

Newsy (Sep. 16, 2014) — President Obama is expected to send 3,000 troops to West Africa as part of the effort to contain Ebola's spread. 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