Increased airway iron as a potential factor in the persistence of<i>Pseudomonas aeruginosa</i>infection in cystic fibrosis

Reid, David W.; Carroll, V. Susan; O'May, C; Champion, AC; Kirov, SM

doi:10.1183/09031936.00154006

Cited by 114 publications

(153 citation statements)

References 29 publications

Supporting

Mentioning

143

Contrasting

Order By: Relevance

“…Furthermore, iron and ferritin levels are positively correlated with c.f.u. of P. aeruginosa and remain elevated after antibiotic treatment of P. aeruginosa infection (Reid et al, 2007). Aspergillus fumigatus co-cultured with macrophages downregulates expression of two cellular iron importers and the iron exporter ferroportin, which, together with an increase in iron retention and ferritin synthesis by the exposed macrophages, provides further evidence of the impact of infection on host iron homeostasis (Seifert et al, 2008).…”

Section: Iron and Cfmentioning

confidence: 86%

“…In a recent study of CF pulmonary exacerbation, patients following treatment with intravenous antibiotics had lower hepcidin and IL-6 levels in serum, increased serum iron, and a trend towards lower sputum iron levels -further evidence of the impact of infection and inflammation on iron metabolism (Gifford et al, 2012). Not surprisingly, given the inflammatory environment of the CF lung, elevated levels of iron and ferritin have been detected in CF sputum by a number of studies (Stites et al, 1998(Stites et al, , 1999Reid et al, 2004Reid et al, , 2007Gray et al, 2010). More recently in a comprehensive study of iron in CF, Ghio et al (2013) demonstrated increased levels of iron and iron-related proteins in bronchoalveolar lavage fluids from CF children, in macrophages of explanted CF lungs and in lung tissue from CF patients -clear evidence of altered iron homeostasis and of iron accumulation in the CF airways (Ghio et al, 2013).…”

Section: Iron and Cfmentioning

confidence: 99%

See 1 more Smart Citation

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Tyrrell¹,

Callaghan²

2016

Microbiology

View full text Add to dashboard Cite

Iron acquisition is vital to microbial survival and is implicated in the virulence of many of the pathogens that reside in the cystic fibrosis (CF) lung. The multifaceted nature of iron acquisition by both bacterial and fungal pathogens encompasses a range of conserved and speciesspecific mechanisms, including secretion of iron-binding siderophores, utilization of siderophores from other species, release of iron from host iron-binding proteins and haemoproteins, and ferrous iron uptake. Pathogens adapt and deploy specific systems depending on iron availability, bioavailability of the iron pool, stage of infection and presence of competing pathogens. Understanding the dynamics of pathogen iron acquisition has the potential to unveil new avenues for therapeutic intervention to treat both acute and chronic CF infections. Here, we examine the range of strategies utilized by the primary CF pathogens to acquire iron and discuss the different approaches to targeting iron acquisition systems as an antimicrobial strategy.

show abstract

Section: Iron and Cfmentioning

confidence: 86%

Section: Iron and Cfmentioning

confidence: 99%

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Tyrrell¹,

Callaghan²

2016

Microbiology

View full text Add to dashboard Cite

show abstract

“…Ferritin is an acute-phase reactant with clinical implications as a serologic marker of acute and chronic inflammation. It often increases during periods of oxidative stress such as acute respiratory distress syndrome (ARDS) 22,23 or cystic fibrosis 24 for the detoxification of free iron, because free iron facilitates the formation of highly toxic hydroxyl radicals from hydrogen peroxide. 25,26 In addition, polymorphisms within the gene that encodes the ferritin light chain are associated with the development of ARDS.…”

Section: Discussionmentioning

confidence: 99%

Serum ferritin and transferrin levels as serologic markers of methylene diphenyl diisocyanate–induced occupational asthma

Hur

Choi

Sheen

et al. 2008

Journal of Allergy and Clinical Immunology

View full text Add to dashboard Cite

Background: Although methylene diphenyl diisocyanate (MDI) may induce occupational asthma in the workplace, the pathogenic mechanisms are unclear. Objectives: By using bronchoalveolar lavage fluid, we sought to identify proteins that were differentially expressed between subjects with MDI-induced occupational asthma (MDI-OA) and asymptomatic exposed controls (AECs). Methods: To find proteins that were differentially expressed between the MDI-OA and AEC groups, 2-dimensional electrophoresis was performed by using bronchoalveolar lavage fluid obtained from subjects after MDI-specific inhalation challenge. The selected protein spots were then identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The clinical relevance of the differentially expressed spots was compared by ELISA using sera from the MDI-OA/eosinophilic bronchitis, AEC, and unexposed healthy control groups. Receiver operating characteristic curves were then plotted, and the sensitivity and specificity were determined. Results: Twenty-three protein spots were identified that distinguished the subjects with MDI-OA from those in the AEC group. Among them, ferritin expression was downregulated whereas transferrin expression was upregulated in subjects with MDI-OA compared with AEC; these results were validated by ELISA using sera from the MDI-OA/EB and AEC groups. To identify subjects with MDI-OA, the optimal serum cutoff levels were 69.84 ng/mL for ferritin and 2.48 mg/mL for transferrin. When these 2 parameters were combined, the sensitivity was 71.43% and the specificity was 85.71%. Conclusion: Serum ferritin and transferrin levels are associated with the phenotype of MDI-OA. (J Allergy Clin Immunol 2008;122:774-80.)

show abstract

“…Iron is not freely available to infectious bacteria in the healthy human airway, because it is predominantly assimilated into iron-binding proteins such as transferrin, lactoferrin, and ferritin, but larger amounts of iron are present in CF lungs (6)(7)(8). Iron in biological environments is commonly present as ferric (Fe 3ϩ ) ions, although the reduced pH (9) and the poor availability of O 2 in the thick mucus layers of CF airways (10,11) may mean that significant amounts of ferrous (Fe 2ϩ ) iron are present.…”

Section: T He Thick Viscous Mucus In the Lungs Of Cystic Fibrosis (Cmentioning

confidence: 99%

Pseudomonas aeruginosa Uses Multiple Pathways To Acquire Iron during Chronic Infection in Cystic Fibrosis Lungs

et al. 2013

View full text Add to dashboard Cite

dPseudomonas aeruginosa chronically infects the lungs of more than 80% of adult patients with cystic fibrosis (CF) and is a major contributor to the progression of disease pathology. P. aeruginosa requires iron for growth and has multiple iron uptake systems that have been studied in bacteria grown in laboratory culture. The purpose of this research was to determine which of these are active during infection in CF. RNA was extracted from 149 sputum samples obtained from 23 CF patients. Reverse transcription-quantitative real-time PCR (RT-qPCR) was used to measure the expression of P. aeruginosa genes encoding transport systems for the siderophores pyoverdine and pyochelin, for heme, and for ferrous ions. Expression of P. aeruginosa genes could be quantified in 89% of the sputum samples. Expression of genes associated with siderophore-mediated iron uptake was detected in most samples but was at low levels in some samples, indicating that other iron uptake mechanisms are active. Expression of genes encoding heme transport systems was also detected in most samples, indicating that heme uptake occurs during infection in CF. feoB expression was detected in all sputum samples, implying an important role for ferrous ion uptake by P. aeruginosa in CF. Our data show that multiple P. aeruginosa iron uptake mechanisms are active in chronic CF infection and that RT-qPCR of RNA extracted from sputum provides a powerful tool for investigating bacterial physiology during infection in CF.

show abstract

Increased airway iron as a potential factor in the persistence ofPseudomonas aeruginosainfection in cystic fibrosis

Cited by 114 publications

References 29 publications

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Iron acquisition in the cystic fibrosis lung and potential for novel therapeutic strategies

Serum ferritin and transferrin levels as serologic markers of methylene diphenyl diisocyanate–induced occupational asthma

Pseudomonas aeruginosa Uses Multiple Pathways To Acquire Iron during Chronic Infection in Cystic Fibrosis Lungs

Contact Info

Product

Resources

About