DNA-fragmentation is a source of bactericidal activity against Pseudomonas aeruginosa
(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:
https://lup.lub.lu.se/record/068c9d1d-edf9-4774-aa59-1afa18f60f16
- author
- Bhongir, Ravi K. V. LU ; Kasetty, Gopinath LU ; Papareddy, Praveen LU ; Mörgelin, Matthias LU ; Herwald, Heiko LU and Egesten, Arne LU
- organization
- publishing date
- 2017-01-20
- 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
- external identifiers
-
- pmid:27784762
- 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
- 2022-04-01 06:05:24
@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 (<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}}, keywords = {{Cystic fibrosis; DNA; DNase trreatment; Pseudomonas aeruginosa; Host defense}}, language = {{eng}}, month = {{01}}, number = {{3}}, pages = {{411--425}}, publisher = {{Portland Press}}, 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}}, doi = {{10.1042/BCJ20160706}}, volume = {{474}}, year = {{2017}}, }