Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection

Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF) patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs) surround the biofilms and create lo...

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Main Authors: Hansen, Christine Rønne, Liengaard, Lars, Kolpen, Mette, Kühl, Michael, Bjarnsholt, Thomas, Moser, Claus, Kharazmi, Arsalan, Pressler, Tanja, Høiby, Niels, Jensen, Peter Østrup
Other Authors: Gulbins, Erich
Format: Article
Language:English
Published: 2014
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Online Access:https://hdl.handle.net/10356/104137
http://hdl.handle.net/10220/19555
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-1041372022-02-16T16:30:30Z Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection Hansen, Christine Rønne Liengaard, Lars Kolpen, Mette Kühl, Michael Bjarnsholt, Thomas Moser, Claus Kharazmi, Arsalan Pressler, Tanja Høiby, Niels Jensen, Peter Østrup Gulbins, Erich Singapore Centre for Environmental Life Sciences Engineering DRNTU::Science::Medicine Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF) patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs) surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS). We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O), an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO3− and NO2− in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 µM N2O (range 1.4–157.9 µM N2O). The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3− decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention. Published version 2014-06-04T04:12:27Z 2019-12-06T21:27:16Z 2014-06-04T04:12:27Z 2019-12-06T21:27:16Z 2014 2014 Journal Article Kolpen, M., Kühl, M., Bjarnsholt, T., Moser, C., Hansen, C. R., Liengaard, L., et al. (2014). Nitrous Oxide Production in Sputum from Cystic Fibrosis Patients with Chronic Pseudomonas aeruginosa Lung Infection. PLoS ONE, 9(1), e84353-. 1932-6203 https://hdl.handle.net/10356/104137 http://hdl.handle.net/10220/19555 10.1371/journal.pone.0084353 24465406 en PLoS ONE © 2014 Kolpen et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Medicine
spellingShingle DRNTU::Science::Medicine
Hansen, Christine Rønne
Liengaard, Lars
Kolpen, Mette
Kühl, Michael
Bjarnsholt, Thomas
Moser, Claus
Kharazmi, Arsalan
Pressler, Tanja
Høiby, Niels
Jensen, Peter Østrup
Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection
description Chronic lung infection by Pseudomonas aeruginosa is the major severe complication in cystic fibrosis (CF) patients, where P. aeruginosa persists and grows in biofilms in the endobronchial mucus under hypoxic conditions. Numerous polymorphonuclear leukocytes (PMNs) surround the biofilms and create local anoxia by consuming the majority of O2 for production of reactive oxygen species (ROS). We hypothesized that P. aeruginosa acquires energy for growth in anaerobic endobronchial mucus by denitrification, which can be demonstrated by production of nitrous oxide (N2O), an intermediate in the denitrification pathway. We measured N2O and O2 with electrochemical microsensors in 8 freshly expectorated sputum samples from 7 CF patients with chronic P. aeruginosa infection. The concentrations of NO3− and NO2− in sputum were estimated by the Griess reagent. We found a maximum median concentration of 41.8 µM N2O (range 1.4–157.9 µM N2O). The concentration of N2O in the sputum was higher below the oxygenated layers. In 4 samples the N2O concentration increased during the initial 6 h of measurements before decreasing for approximately 6 h. Concomitantly, the concentration of NO3− decreased in sputum during 24 hours of incubation. We demonstrate for the first time production of N2O in clinical material from infected human airways indicating pathogenic metabolism based on denitrification. Therefore, P. aeruginosa may acquire energy for growth by denitrification in anoxic endobronchial mucus in CF patients. Such ability for anaerobic growth may be a hitherto ignored key aspect of chronic P. aeruginosa infections that can inform new strategies for treatment and prevention.
author2 Gulbins, Erich
author_facet Gulbins, Erich
Hansen, Christine Rønne
Liengaard, Lars
Kolpen, Mette
Kühl, Michael
Bjarnsholt, Thomas
Moser, Claus
Kharazmi, Arsalan
Pressler, Tanja
Høiby, Niels
Jensen, Peter Østrup
format Article
author Hansen, Christine Rønne
Liengaard, Lars
Kolpen, Mette
Kühl, Michael
Bjarnsholt, Thomas
Moser, Claus
Kharazmi, Arsalan
Pressler, Tanja
Høiby, Niels
Jensen, Peter Østrup
author_sort Hansen, Christine Rønne
title Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection
title_short Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection
title_full Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection
title_fullStr Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection
title_full_unstemmed Nitrous oxide production in sputum from cystic fibrosis patients with chronic Pseudomonas aeruginosa lung infection
title_sort nitrous oxide production in sputum from cystic fibrosis patients with chronic pseudomonas aeruginosa lung infection
publishDate 2014
url https://hdl.handle.net/10356/104137
http://hdl.handle.net/10220/19555
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