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|
American Society for Microbiology