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DNA-fragmentation is a source of bactericidal activity against Pseudomonas aeruginosa

Bhongir, Ravi K. V. LU ; Kasetty, Gopinath LU ; Papareddy, Praveen LU ; Mörgelin, Matthias LU ; Herwald, Heiko LU and Egesten, Arne LU (2017) In Biochemical Journal 474(3). p.411-425
Abstract
Pseudomonas aeruginosa airway infection is common in cystic fibrosis (CF), a disease
also characterized by abundant extracellular DNA (eDNA) in the airways. The eDNA is
mainly derived from neutrophils accumulating in the airways and contributes to a high
sputum viscosity. The altered environment in the lower airways also paves the way for
chronic P. aeruginosa infection. Here, we show that mice with P. aeruginosa airway infection have increased survival and decreased bacterial load after topical treatment with DNase. Furthermore, DNA from the sputum of CF patients showed increased bactericidal activity after treatment with DNase ex vivo. Both degraded DNA of neutrophil extracellular traps (NETs) and genomic DNA degraded by... (More)
Pseudomonas aeruginosa airway infection is common in cystic fibrosis (CF), a disease
also characterized by abundant extracellular DNA (eDNA) in the airways. The eDNA is
mainly derived from neutrophils accumulating in the airways and contributes to a high
sputum viscosity. The altered environment in the lower airways also paves the way for
chronic P. aeruginosa infection. Here, we show that mice with P. aeruginosa airway infection have increased survival and decreased bacterial load after topical treatment with DNase. Furthermore, DNA from the sputum of CF patients showed increased bactericidal activity after treatment with DNase ex vivo. Both degraded DNA of neutrophil extracellular traps (NETs) and genomic DNA degraded by serum, acquired bactericidal activity against P. aeruginosa. In vitro, small synthetic DNA-fragments (<100 base pairs) but not large fragments nor genomic DNA, were bactericidal against Gram-negative but not Grampositive bacteria. The addition of divalent cations reduced bacterial killing, suggesting that chelation of divalent cations by DNA results in destabilization of the lipopolysaccharide (LPS) envelope. This is a novel antibacterial strategy where fragmentation of eDNA and DNA-fragments can be used to treat P. aeruginosa airway infection. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cystic fibrosis, DNA, DNase trreatment, Pseudomonas aeruginosa, Host defense
in
Biochemical Journal
volume
474
issue
3
pages
411 - 425
publisher
Portland Press Limited
external identifiers
  • scopus:85014711528
  • wos:000393768400006
ISSN
0264-6021
DOI
10.1042/BCJ20160706
language
English
LU publication?
yes
id
068c9d1d-edf9-4774-aa59-1afa18f60f16
alternative location
https://www.ncbi.nlm.nih.gov/pubmed/27784762
date added to LUP
2017-02-01 15:00:24
date last changed
2018-01-07 11:47:42
@article{068c9d1d-edf9-4774-aa59-1afa18f60f16,
  abstract     = {Pseudomonas aeruginosa airway infection is common in cystic fibrosis (CF), a disease<br>
also characterized by abundant extracellular DNA (eDNA) in the airways. The eDNA is<br>
mainly derived from neutrophils accumulating in the airways and contributes to a high<br>
sputum viscosity. The altered environment in the lower airways also paves the way for<br>
chronic P. aeruginosa infection. Here, we show that mice with P. aeruginosa airway infection have increased survival and decreased bacterial load after topical treatment with DNase. Furthermore, DNA from the sputum of CF patients showed increased bactericidal activity after treatment with DNase ex vivo. Both degraded DNA of neutrophil extracellular traps (NETs) and genomic DNA degraded by serum, acquired bactericidal activity against P. aeruginosa. In vitro, small synthetic DNA-fragments (&lt;100 base pairs) but not large fragments nor genomic DNA, were bactericidal against Gram-negative but not Grampositive bacteria. The addition of divalent cations reduced bacterial killing, suggesting that chelation of divalent cations by DNA results in destabilization of the lipopolysaccharide (LPS) envelope. This is a novel antibacterial strategy where fragmentation of eDNA and DNA-fragments can be used to treat P. aeruginosa airway infection.},
  author       = {Bhongir, Ravi K. V.  and Kasetty, Gopinath and Papareddy, Praveen and Mörgelin, Matthias and Herwald, Heiko and Egesten, Arne},
  issn         = {0264-6021},
  keyword      = {Cystic fibrosis,DNA,DNase trreatment,Pseudomonas aeruginosa,Host defense},
  language     = {eng},
  month        = {01},
  number       = {3},
  pages        = {411--425},
  publisher    = {Portland Press Limited},
  series       = {Biochemical Journal},
  title        = {DNA-fragmentation is a source of bactericidal activity against <i>Pseudomonas aeruginosa</i>},
  url          = {http://dx.doi.org/10.1042/BCJ20160706},
  volume       = {474},
  year         = {2017},
}