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