Navigation Links
Target 2 forms of iron to control cystic fibrosis lung infection
Date:8/19/2013

The bacterium Pseudomonas aeruginosa needs iron to establish and maintain a biofilm in the lungs of cystic fibrosis patients, and therapies have been proposed to deprive the bacteria of this necessary element. However, these techniques may not work, according to a new study published in mBio, the online open-access journal of the American Society for Microbiology, because they only target one of the two types of iron that are available in the lung.

Current therapies focus on removing ferric iron [Fe(III)] but leave plenty of ferrous iron [Fe(II)] behind for the bacteria to use, according to the study. The concentration of Fe(II) present in the lungs of patients with cystic fibrosis correlates with disease severity, a sign that pathogens not only use ferrous iron - they thrive on it. These findings could have implications for treatment of P. aeruginosa in patients with cystic fibrosis.

"It is clear that the percentage of the total iron pool that is Fe(II) is substantial, particularly in severely ill patients," write the authors. Despite a wealth of data on the abundance of iron in the airways of patients with cystic fibrosis, this study is the first to make direct measurements of two different bioavailable forms of iron, Fe(III) and Fe(II).

An optimal concentration of bioavailable iron is needed to establish the formation of P. aeruginosa biofilms, thick accumulations of bacteria, polysaccharides, and cellular debris that can build up in the lungs of cystic fibrosis patients. It's also integral to stabilizing biofilms, so therapies have been proposed to perturb P. aeruginosa's uptake and acquisition of iron to fight biofilm development in the lung.

Because Fe(III) is commonly assumed to be the dominant physiologically-relevant form of iron, therapies focus on blocking Fe(III) acquisition. However, Fe(II) may also be present in the lung, reasoned the authors, a fact that could undermine iron-targeting therapies.

They tested sputum samples from a cross-section of 33 cystic fibrosis patients from the US and Belgium. Fe(II) was, indeed, abundant in the lungs of cystic fibrosis patients, and it comprised a considerable amount of the total iron in each sample, confirming the authors' suspicions. What's more, sicker patients had greater quantities of Fe(II), and while Fe(II) concentration was significantly correlated with disease the concentration of Fe(III) was not.

The authors also tested whether inhibiting the uptake of Fe(II) or Fe(III) - or both - would prevent biofilm formation. Using a high-throughput biofilm assay in the lab, they tested the ability of ferrozine, an Fe(II)-specific chelator, and conalbumin, a Fe(III)-specific chelator, to bind iron and prevent the buildup of a biofilm. They found that in a system where both Fe(II) and Fe(III) are present, as they are in the lungs of cystic fibrosis patients, it was most effective to apply both types of chelators: sequestering both forms of iron resulted in a 58% reduction in biofilm accumulation. This suggests that for treating patients, targeting both forms of iron might be more effective than targeting Fe(III) alone.

"Collectively, these studies underscore the importance of a dialectic between laboratory and environmental studies of pathogens such as P. aeruginosa," write the authors. Mechanistic studies of microorganisms in the laboratory can only go so far without real-world information about the chemical conditions under which they live in the human body. The integrated approach used in this study has provided a superior understanding of how iron availability might be manipulated to prevent biofilm formation and can inform the effective design and application of therapeutic strategies for treating P. aeruginosa biofilms.


'/>"/>

Contact: Jim Sliwa
jsliwa@asmusa.org
202-942-9297
American Society for Microbiology
Source:Eurekalert

Related biology news :

1. Collaborative preclinical efficacy studies suggest a new target for drug addiction treatment
2. Crestor Delivers Latest LDL-C Targets in High-Risk Patients at Lower Doses than Other Statins
3. Scripps Research Institute scientists find promising vaccine targets on hepatitis C virus
4. Nanobubbles plus chemotherapy equals single-cell cancer targeting
5. Researchers identify Achilles heel of dengue virus, target for future vaccines
6. Scientists identify FLT3 gene as a valid therapeutic target in acute myeloid leukemia
7. Genetically modified corn affects its symbiotic relationship with non-target soil organisms
8. Unique adaptations to a symbiotic lifestyle reveal novel targets for aphid insecticides
9. Yeast cell reaction to Zoloft suggests alternative cause, drug target for depression
10. Key proteins newly discovered form and function may provide novel cancer treatment target
11. Scientists discover new inflammatory target
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/14/2016)... , April 14, 2016 ... and Malware Detection, today announced the appointment of ... the new role. Goldwerger,s leadership appointment comes ... the heels of the deployment of its platform at ... behavioral biometric technology, which discerns unique cognitive and physiological ...
(Date:3/31/2016)... , March 31, 2016 ... ) ("LegacyXChange" or the "Company") LegacyXChange is ... users of its soon to be launched online site ... https://www.youtube.com/channel/UCyTLBzmZogV1y2D6bDkBX5g ) will also provide potential shareholders ... of DNA technology to an industry that is notorious ...
(Date:3/29/2016)... Florida , March 29, 2016 ... the "Company") LegacyXChange "LEGX" and SelectaDNA/CSI Protect are pleased ... in ink used in a variety of writing instruments, ... Buyers of originally created collectibles from athletes on LegacyXChange ... forensic analysis of the DNA. Bill ...
Breaking Biology News(10 mins):
(Date:5/2/2016)... 2, 2016 Q BioMed Inc. ... partner Mannin Research Inc. will be attending the Association ... place from May 1-5, 2016 in Seattle ... with its vendors and research partners. The meeting provides ... and other collaborative opportunities for the MAN-01 program for ...
(Date:4/29/2016)... , ... April 29, 2016 , ... ... personalized pain medicine, is excited to announce the launch of the Proove ... health studies, volunteerism, and education to promote the use of personalized medicine for ...
(Date:4/29/2016)... (PRWEB) , ... April 29, 2016 , ... Intelligent Implant ... by the FDA via 510(k) for sale in the United States. These components ... posterior thoraco-lumbar fusions. With one-level sales beginning in October of 2015, the company ...
(Date:4/28/2016)... ... 2016 , ... Next week on May 5 at 2:55 ... for tissue stem cell counting and expansion to gene-editing scientists and other attendees ... Genome Engineering in Burlington, Massachusetts. , The attention of most gene-editing scientists appears ...
Breaking Biology Technology: