Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. / Kragh, Kasper Nørskov; Alhede, Morten; Jensen, Peter Østrup; Moser, Claus Ernst; Scheike, Thomas; Jacobsen, Carsten S.; Poulsen, Steen Seier; Eickhardt-Sørensen, Steffen Robert; Trostrup, Hannah; Christoffersen, Lars; Hougen, Hans Petter; Rickelt, Lars F.; Kühl, Michael; Høiby, Niels; Bjarnsholt, Thomas.

In: Infection and Immunity, Vol. 82, No. 11, 2014, p. 4477-4486.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Kragh, KN, Alhede, M, Jensen, PØ, Moser, CE, Scheike, T, Jacobsen, CS, Poulsen, SS, Eickhardt-Sørensen, SR, Trostrup, H, Christoffersen, L, Hougen, HP, Rickelt, LF, Kühl, M, Høiby, N & Bjarnsholt, T 2014, 'Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients', Infection and Immunity, vol. 82, no. 11, pp. 4477-4486. https://doi.org/10.1128/IAI.01969-14

APA

Kragh, K. N., Alhede, M., Jensen, P. Ø., Moser, C. E., Scheike, T., Jacobsen, C. S., Poulsen, S. S., Eickhardt-Sørensen, S. R., Trostrup, H., Christoffersen, L., Hougen, H. P., Rickelt, L. F., Kühl, M., Høiby, N., & Bjarnsholt, T. (2014). Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. Infection and Immunity, 82(11), 4477-4486. https://doi.org/10.1128/IAI.01969-14

Vancouver

Kragh KN, Alhede M, Jensen PØ, Moser CE, Scheike T, Jacobsen CS et al. Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. Infection and Immunity. 2014;82(11):4477-4486. https://doi.org/10.1128/IAI.01969-14

Author

Kragh, Kasper Nørskov ; Alhede, Morten ; Jensen, Peter Østrup ; Moser, Claus Ernst ; Scheike, Thomas ; Jacobsen, Carsten S. ; Poulsen, Steen Seier ; Eickhardt-Sørensen, Steffen Robert ; Trostrup, Hannah ; Christoffersen, Lars ; Hougen, Hans Petter ; Rickelt, Lars F. ; Kühl, Michael ; Høiby, Niels ; Bjarnsholt, Thomas. / Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients. In: Infection and Immunity. 2014 ; Vol. 82, No. 11. pp. 4477-4486.

Bibtex

@article{24588e808d2c487eae55459b9487ef73,
title = "Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients",
abstract = "Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the in vivo growth physiology of P. aeruginosa within lungs of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF patients and the growth rates of P. aeruginosa in infected lungs in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also observed in vitro, where this limitation was alleviated in the presence of the alternative electron acceptor nitrate. The finding that P. aeruginosa growth patterns correlate with the number of surrounding PMNs points to a bacteriostatic effect by PMNs via their strong O2 consumption, which slows the growth of P. aeruginosa in infected CF lungs. In support of this, the growth of P. aeruginosa was significantly higher in the respiratory airways than in the conducting airways of mice. These results indicate a complex host-pathogen interaction in chronic P. aeruginosa infection of the CF lung whereby PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration.",
keywords = "Adult, Animals, Biofilms, Cystic Fibrosis, Female, Humans, In Situ Hybridization, Fluorescence, Lung Diseases, Male, Mice, Mice, Inbred BALB C, Neutrophils, Peptide Nucleic Acids, Pseudomonas Infections, Pseudomonas aeruginosa",
author = "Kragh, {Kasper N{\o}rskov} and Morten Alhede and Jensen, {Peter {\O}strup} and Moser, {Claus Ernst} and Thomas Scheike and Jacobsen, {Carsten S.} and Poulsen, {Steen Seier} and Eickhardt-S{\o}rensen, {Steffen Robert} and Hannah Trostrup and Lars Christoffersen and Hougen, {Hans Petter} and Rickelt, {Lars F.} and Michael K{\"u}hl and Niels H{\o}iby and Thomas Bjarnsholt",
note = "Copyright {\textcopyright} 2014, American Society for Microbiology. All Rights Reserved.",
year = "2014",
doi = "10.1128/IAI.01969-14",
language = "English",
volume = "82",
pages = "4477--4486",
journal = "Infection and Immunity",
issn = "0019-9567",
publisher = "American Society for Microbiology",
number = "11",

}

RIS

TY - JOUR

T1 - Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients

AU - Kragh, Kasper Nørskov

AU - Alhede, Morten

AU - Jensen, Peter Østrup

AU - Moser, Claus Ernst

AU - Scheike, Thomas

AU - Jacobsen, Carsten S.

AU - Poulsen, Steen Seier

AU - Eickhardt-Sørensen, Steffen Robert

AU - Trostrup, Hannah

AU - Christoffersen, Lars

AU - Hougen, Hans Petter

AU - Rickelt, Lars F.

AU - Kühl, Michael

AU - Høiby, Niels

AU - Bjarnsholt, Thomas

N1 - Copyright © 2014, American Society for Microbiology. All Rights Reserved.

PY - 2014

Y1 - 2014

N2 - Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the in vivo growth physiology of P. aeruginosa within lungs of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF patients and the growth rates of P. aeruginosa in infected lungs in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also observed in vitro, where this limitation was alleviated in the presence of the alternative electron acceptor nitrate. The finding that P. aeruginosa growth patterns correlate with the number of surrounding PMNs points to a bacteriostatic effect by PMNs via their strong O2 consumption, which slows the growth of P. aeruginosa in infected CF lungs. In support of this, the growth of P. aeruginosa was significantly higher in the respiratory airways than in the conducting airways of mice. These results indicate a complex host-pathogen interaction in chronic P. aeruginosa infection of the CF lung whereby PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration.

AB - Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the in vivo growth physiology of P. aeruginosa within lungs of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF patients and the growth rates of P. aeruginosa in infected lungs in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also observed in vitro, where this limitation was alleviated in the presence of the alternative electron acceptor nitrate. The finding that P. aeruginosa growth patterns correlate with the number of surrounding PMNs points to a bacteriostatic effect by PMNs via their strong O2 consumption, which slows the growth of P. aeruginosa in infected CF lungs. In support of this, the growth of P. aeruginosa was significantly higher in the respiratory airways than in the conducting airways of mice. These results indicate a complex host-pathogen interaction in chronic P. aeruginosa infection of the CF lung whereby PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration.

KW - Adult

KW - Animals

KW - Biofilms

KW - Cystic Fibrosis

KW - Female

KW - Humans

KW - In Situ Hybridization, Fluorescence

KW - Lung Diseases

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Neutrophils

KW - Peptide Nucleic Acids

KW - Pseudomonas Infections

KW - Pseudomonas aeruginosa

U2 - 10.1128/IAI.01969-14

DO - 10.1128/IAI.01969-14

M3 - Journal article

C2 - 25114118

VL - 82

SP - 4477

EP - 4486

JO - Infection and Immunity

JF - Infection and Immunity

SN - 0019-9567

IS - 11

ER -

ID: 135152100