Nitric oxide metabolites in cystic fibrosis lung disease

Grasemann, Hartmut; Ioannidis, I; Tomkiewicz, R.P.; Groot, Herbert de; Rubin, Bruce K.; Ratjen, Félix

doi:10.1136/adc.78.1.49

Cited by 138 publications

(141 citation statements)

References 27 publications

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“…For example, synergistic and antagonistic behavior between different CF pathogens has been described (Duan et al, 2003;Harrison, 2007;Sibley et al, 2008;Mitchell et al, 2010;Yang et al, 2011;Venkataraman et al, 2014), and the microbial community has been proposed to contain stable and disturbed states, much like those in classical ecology (Conrad et al, 2012). Known chemical characteristics of the CF lung include lowered pH (Tate et al, 2002;Pezzulo et al, 2012), low oxygen tensions (Worlitzsch et al, 2002) and high levels of amino acids, nitrate, iron and phenazines (Grasemann et al, 1998;Jones et al, 2000;Palmer et al, 2007;Ghio et al, 2012;Hunter et al, 2012). In the environment, microbial communities are known to stratify based on oxygen and other chemical gradients (Fenchel and Finlay, 2008;Morris and Schmidt, 2013).…”

Section: Introductionmentioning

confidence: 99%

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

et al. 2014

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There is a poor understanding of how the physiology of polymicrobial communities in cystic fibrosis (CF) lungs contributes to pulmonary exacerbations and lung function decline. In this study, a microbial culture system based on the principles of the Winogradsky column (WinCF system) was developed to study the physiology of CF microbes. The system used glass capillary tubes filled with artificial sputum medium to mimic a clogged airway bronchiole. Chemical indicators were added to observe microbial physiology within the tubes. Characterization of sputum samples from seven patients showed variation in pH, respiration, biofilm formation and gas production, indicating that the physiology of CF microbial communities varied among patients. Incubation of homogenized tissues from an explant CF lung mirrored responses of a Pseudomonas aeruginosa pure culture, supporting evidence that end-stage lungs are dominated by this pathogen. Longitudinal sputum samples taken through two exacerbation events in a single patient showed that a two-unit drop in pH and a 30% increase in gas production occurred in the tubes prior to exacerbation, which was reversed with antibiotic treatment. Microbial community profiles obtained through amplification and sequencing of the 16S rRNA gene showed that fermentative anaerobes became more abundant during exacerbation and were then reduced during treatment where P. aeruginosa became the dominant bacterium. Results from the WinCF experiments support the model where two functionally different CF microbial communities exist, the persistent Climax Community and the acute Attack Community. Fermentative anaerobes are hypothesized to be the core members of the Attack Community and production of acidic and gaseous products from fermentation may drive developing exacerbations. Treatment targeting the Attack Community may better resolve exacerbations and resulting lung damage.

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Section: Introductionmentioning

confidence: 99%

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

et al. 2014

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“…Persistent inflammation and repeated cycles of infection are present in CF lungs, resulting in progressive lung damage and pulmonary fibrosis (25). Even in stable patients, chronic airway inflammation is present, as reflected by high airway fluid concentrations of proinflammatory cytokines (26). Analysis of BAL fluid has shown a 1.000-fold increase in the number of neutrophils from the lungs of patients with CF compared with controls (27).…”

Section: Discussionmentioning

confidence: 99%

Metabolomics of Volatile Organic Compounds in Cystic Fibrosis Patients and Controls

et al. 2010

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ABSTRACT:In cystic fibrosis (CF), airway inflammation causes an increased production of reactive oxygen species, responsible for degradation of cell membranes. During this process, volatile organic compounds (VOCs) are formed. Measurement of VOCs in exhaled breath of CF patients may be useful for the assessment of airway inflammation. This study investigates whether "metabolomics' of VOCs could discriminate between CF and controls, and between CF patients with and without Pseudomonas colonization. One hundred five children (48 with CF, 57 controls) were included in this study. After exhaled breath collection, samples were transferred onto tubes containing active carbon to adsorb and stabilize VOCs. Samples were analyzed by gas chromatography-time of flight-mass spectrometry to assess VOC profiles. Analysis showed that 1099 VOCs had a prevalence of at least 7%. By using 22 VOCs, a 100% correct identification of CF patients and controls was possible. With 10 VOCs, 92% of the subjects were correctly classified. The reproducibility of VOC measurements with a 1-h interval was very good (match factor 0.90 Ϯ 0.038). We conclude that metabolomics of VOCs in exhaled breath was possible in a reproducible way. This new technique was able to discriminate not only between CF patients and controls but also between CF patients with or without Pseudomonas colonization. (Pediatr Res 68: 75-80, 2010)

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“…Previously, our laboratory reported that H 2 O 2 -producing oral commensal streptococci can inhibit P. aeruginosa in a nitritedependent manner through the production of reactive (Scoffield & Wu, 2015). Nitrite is readily available within the oral cavity and CF lung, and is a byproduct of denitrifying bacteria (Grasemann et al, 1998;Hezel & Weitzberg, 2015). Nitrite reductase is one of several enzymes unique to the denitrification pathway of P. aeruginosa and is responsible for catalysing the reduction of nitrite to nitric oxide.…”

Section: Introductionmentioning

confidence: 99%

Nitrite reductase is critical for Pseudomonas aeruginosa survival during co-infection with the oral commensal Streptococcus parasanguinis

Scoffield

2016

Microbiology

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Pseudomonas aeruginosa is the major aetiological agent of chronic pulmonary infections in cystic fibrosis (CF) patients. However, recent evidence suggests that the polymicrobial community of the CF lung may also harbour oral streptococci, and colonization by these micro-organisms may have a negative impact on P. aeruginosa within the CF lung. Our previous studies demonstrated that nitrite abundance plays an important role in P. aeruginosa survival during co-infection with oral streptococci. Nitrite reductase is a key enzyme involved in nitrite metabolism. Therefore, the objective of this study was to examine the role nitrite reductase (gene nirS) plays in P. aeruginosa survival during co-infection with an oral streptococcus, Streptococcus parasanguinis. Inactivation of nirS in both the chronic CF isolate FRD1 and acute wound isolate PAO1 reduced the survival rate of P. aeruginosa when co-cultured with S. parasanguinis. Growth of both mutants was restored when co-cultured with S. parasanguinis that was defective for H 2 O 2 production. Furthermore, the nitrite reductase mutant was unable to kill Drosophila melanogaster during co-infection with S. parasanguinis. Taken together, these results suggest that nitrite reductase plays an important role for survival of P. aeruginosa during co-infection with S. parasanguinis.

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Nitric oxide metabolites in cystic fibrosis lung disease

Cited by 138 publications

References 27 publications

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

A Winogradsky-based culture system shows an association between microbial fermentation and cystic fibrosis exacerbation

Metabolomics of Volatile Organic Compounds in Cystic Fibrosis Patients and Controls

Nitrite reductase is critical for Pseudomonas aeruginosa survival during co-infection with the oral commensal Streptococcus parasanguinis

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