Featured Research

from universities, journals, and other organizations

Two-pronged Model Could Help Foil Tough Cystic Fibrosis Infections

Date:
May 1, 2009
Source:
Dartmouth College
Summary:
Researchers have devised a new way to thwart the relentless bacterial infections that thrive in the lungs of people with cystic fibrosis, unlocking new possibilities against a tenacious and toxic hallmark of the common genetic disease.

Dr. Sophie Moreau-Marquis.
Credit: Image courtesy of Dartmouth College

Dartmouth Medical School researchers have devised a novel approach for thwarting the relentless bacterial infections that thrive in the lungs of people with cystic fibrosis (CF), unlocking new possibilities against a tenacious and toxic hallmark of the common genetic disease.

Related Articles


Combining a mainstay antibiotic with drugs to deprive the bacteria of iron, which facilitates their persistent growth, appears to boost infection killing, they found.

Their research, reported in the American Journal of Respiratory Cell and Molecular Biology online and scheduled for publication, builds on the collaborative expertise of DMS microbiology and lung physiology labs studying cystic fibrosis infections.

Cystic fibrosis patients are plagued by infections of the bacteria Pseudomonas aeruginosa. Their mucous-clogged lungs are fertile incubators for the bacteria to breed and cluster in slimy communities called biofilms that become increasingly drug resistant and damaging. Tobramycin, the antibiotic routinely used against the microbes, can control, but not efficiently eliminate Pseudomonas established on CF airway cells.

Last year, the DMS researchers reported that it took far more tobramycin to destroy biofilm pockets than can be delivered to the lungs. Using a surrogate tissue culture system they created to simulate human airways, they determined that up to 10 times the maximum tobramycin dosage was needed. They were also studying iron overload in CF lungs. Airway cells with the CF gene mutation release more iron, and the bacteria depend on that iron to form their resilient biofilms, the investigators discovered.

Now, applying their findings to the clinical front, the team demonstrated that two agents already approved by the Federal Drug Administration to treat acute iron poisoning or overload can enhance the ability of tobramycin against Pseudomonas infection.

"The beauty is that we are mixing FDA-approved drugs-- antibiotics and iron chelators-- to potentiate the effect of tobramycin on biofilm formation," said lead author Dr. Sophie Moreau-Marquis, a research associate. "It's an exciting translational framework that opens the door to potentially treating CF patients, taking the novel model we developed from the lab hopefully to the clinic."

Co-authors of the study are DMS professors Dr. Bruce Stanton of physiology, who heads the laboratory where Moreau-Marquis works, and Dr. George O'Toole of microbiology and immunology.

The research combines two results: "We were first to show iron is definitive for biofilms forming on live human airway cells. And the highest concentration of tobramycin that can reach CF lungs is below what we've shown to be barely enough to eradicate biofilms on airway cells," Moreau-Marquis said.

The team used two FDA-approved iron chelators, deferoxamine and deferasirox, that can remove excess iron from the system by binding to the metal in a process called chelation. To mimic the clinical environment, they stuck to the maximum possible tobramycin dose of 1,000 micrograms per milliliter, mixed with a chelator.

The combination had a dramatic effect: it disrupted the mass of established and highly resistant bacteria in human airway cells by 90 percent and it also prevented formation of damaging biofilms. In contrast, neither an iron chelator nor tobramycin alone had such success.

"We built on the idea that if more iron helps bacteria to grow, maybe taking iron away will help kill them," said O'Toole. "The concept is to reformulate one of these iron chelators to be inhaled with tobramycin, which is already inhalable, to treat the bacteria locally in the lungs."

Still, the team found evidence that a chelator can get into lungs from the bloodstream. Using a permeable support in the lab, they mimicked giving tobramycin to the lung side and a chelator to the blood side and showed that the iron chelator is able to work its way through to lungs.

The researchers are working with the CF clinic at Dartmouth-Hitchcock Medical Center to develop clinical trials. Their study is part of Dartmouth's interdisciplinary Lung Biology and Cystic Fibrosis Research Development programs, and is supported by the National Institutes of Health and the Cystic Fibrosis Foundation.


Story Source:

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


Journal Reference:

  1. Sophie Moreau-Marquis, George A O'Toole, and Bruce A Stanton. Tobramycin and FDA-approved Iron Chelators Eliminate P. aeruginosa Biofilms on Cystic Fibrosis Cells. American Journal of Respiratory Cell and Molecular Biology, 2009; DOI: 10.1165/rcmb.2008-0299OC

Cite This Page:

Dartmouth College. "Two-pronged Model Could Help Foil Tough Cystic Fibrosis Infections." ScienceDaily. ScienceDaily, 1 May 2009. <www.sciencedaily.com/releases/2009/04/090424114653.htm>.
Dartmouth College. (2009, May 1). Two-pronged Model Could Help Foil Tough Cystic Fibrosis Infections. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2009/04/090424114653.htm
Dartmouth College. "Two-pronged Model Could Help Foil Tough Cystic Fibrosis Infections." ScienceDaily. www.sciencedaily.com/releases/2009/04/090424114653.htm (accessed October 31, 2014).

Share This



More Health & Medicine News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Melafind: Spotting Melanoma Without a Biopsy

Melafind: Spotting Melanoma Without a Biopsy

Ivanhoe (Oct. 31, 2014) The MelaFind device is a pain-free way to check suspicious moles for melanoma, without the need for a biopsy. Video provided by Ivanhoe
Powered by NewsLook.com
Battling Multiple Myeloma

Battling Multiple Myeloma

Ivanhoe (Oct. 31, 2014) The answer isn’t always found in new drugs – repurposing an ‘old’ drug that could mean better multiple myeloma treatment, and hope. Video provided by Ivanhoe
Powered by NewsLook.com
Chronic Inflammation and Prostate Cancer

Chronic Inflammation and Prostate Cancer

Ivanhoe (Oct. 31, 2014) New information that is linking chronic inflammation in the prostate and prostate cancer, which may help doctors and patients prevent cancer in the future. Video provided by Ivanhoe
Powered by NewsLook.com
Sickle Cell: Stopping Kids’ Silent Strokes

Sickle Cell: Stopping Kids’ Silent Strokes

Ivanhoe (Oct. 31, 2014) Blood transfusions are proving crucial to young sickle cell patients by helping prevent strokes, even when there is no outward sign of brain injury. Video provided by Ivanhoe
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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