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.
mBio® is an open access online journal published by the American Society for Microbiology to make microbiology research broadly accessible. The focus of the journal is on rapid publication of cutting-edge research spanning the entire spectrum of microbiology and related fields. It can be found online at http://mbio.asm.org.
The American Society for Microbiology is the largest single life science society, composed of over 39,000 scientists and health professionals. ASM's mission is to advance the microbiological sciences as a vehicle for understanding life processes and to apply and communicate this knowledge for the improvement of health and environmental and economic well-being worldwide.
Jim Sliwa | EurekAlert!
More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn
How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau
On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.
We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...
What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...
For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.
Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...
At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.
No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...
Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.
Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...
08.01.2018 | Event News
11.12.2017 | Event News
08.12.2017 | Event News
19.01.2018 | Materials Sciences
19.01.2018 | Health and Medicine
19.01.2018 | Physics and Astronomy