TY - JOUR

T1 - Extracellular DNA and F-actin as targets in antibiofilm cystic fibrosis therapy

AU - Tolker-Nielsen, Tim

AU - Høiby, Niels

PY - 2009

Y1 - 2009

N2 - Evaluation of: Parks QM, Young RL, Poch KR, Malcolm KC, Vasil ML, Nick JA: Neutrophil enhancement of Pseudomonas aeruginosa biofilm development: human F-actin and DNA as targets for therapy. J. Med. Microbiol. 58(4), 492-502 (2009). Pseudomonas aeruginosa infection and biofilm formation in the cystic fibrosis lung occurs in association with an exuberant inflammatory response in a neutrophil-rich environment. The presence of DNA/F-actin bundles, formed by components released from necrotic neutrophils, was shown to stimulate biofilm formation by P. aeruginosa. Soluble polyvalent anions can sequester polyvalent cations and dissolve DNA/F-actin bundles, and treatment with polyvalent anions was shown to disrupt neutrophil-induced P. aeruginosa biofilms. In addition, polyvalent anions could also prevent the formation of neutrophil-induced P. aeruginosa biofilms. While young neutrophil-induced P. aeruginosa biofilms could be disrupted by treatment with polyvalent anions or DNase, older neutrophil-induced biofilms, or biofilms formed by a mucoid P. aeruginosa variant, were less susceptible to treatment with polyvalent anions or DNase, but they could be efficiently disrupted by polyvalent anion-DNase combination treatment. The synergistic effect of the combined polyvalent anion-DNase treatment is most likely due to the capacity of polyvalent anions to dissociate DNA/F-actin bundles with bacteria and polysaccharides, leading to exposure of a greater number of DNase cleavage sites on the extracellular DNA. It is conceivable that treatment with soluble polyvalent anions as an adjunct to DNase treatment will represent an improvement in cystic fibrosis therapy.

AB - Evaluation of: Parks QM, Young RL, Poch KR, Malcolm KC, Vasil ML, Nick JA: Neutrophil enhancement of Pseudomonas aeruginosa biofilm development: human F-actin and DNA as targets for therapy. J. Med. Microbiol. 58(4), 492-502 (2009). Pseudomonas aeruginosa infection and biofilm formation in the cystic fibrosis lung occurs in association with an exuberant inflammatory response in a neutrophil-rich environment. The presence of DNA/F-actin bundles, formed by components released from necrotic neutrophils, was shown to stimulate biofilm formation by P. aeruginosa. Soluble polyvalent anions can sequester polyvalent cations and dissolve DNA/F-actin bundles, and treatment with polyvalent anions was shown to disrupt neutrophil-induced P. aeruginosa biofilms. In addition, polyvalent anions could also prevent the formation of neutrophil-induced P. aeruginosa biofilms. While young neutrophil-induced P. aeruginosa biofilms could be disrupted by treatment with polyvalent anions or DNase, older neutrophil-induced biofilms, or biofilms formed by a mucoid P. aeruginosa variant, were less susceptible to treatment with polyvalent anions or DNase, but they could be efficiently disrupted by polyvalent anion-DNase combination treatment. The synergistic effect of the combined polyvalent anion-DNase treatment is most likely due to the capacity of polyvalent anions to dissociate DNA/F-actin bundles with bacteria and polysaccharides, leading to exposure of a greater number of DNase cleavage sites on the extracellular DNA. It is conceivable that treatment with soluble polyvalent anions as an adjunct to DNase treatment will represent an improvement in cystic fibrosis therapy.

U2 - 10.2217/fmb.09.38

DO - 10.2217/fmb.09.38

M3 - Journal article

C2 - 19659420

VL - 4

SP - 645

EP - 647

JO - Future Microbiology

JF - Future Microbiology

SN - 1746-0913

ER -