Neutrophil enhancement of Pseudomonas aeruginosa biofilm development: human F-actin and DNA as targets for therapy
- 1 April 2009
- journal article
- Published by Microbiology Society in Journal of Medical Microbiology
- Vol. 58 (4), 492-502
- https://doi.org/10.1099/jmm.0.005728-0
Abstract
In the cystic fibrosis (CF) airway, chronic infection by Pseudomonas aeruginosa results from biofilm formation in a neutrophil-rich environment. We tested the capacity of human neutrophils to modify early biofilm formation of P. aeruginosa strain PAO1, and an isogenic CF strain isolated early and years later in infection. In a static reactor, P. aeruginosa biofilm density of all strains was enhanced at 24 h in the presence of neutrophils, with the greatest relative increase associated with the lowest inoculum of P. aeruginosa tested. Previously, neutrophil-induced biofilm enhancement was shown to largely result from the incorporation of F-actin and DNA polymers into the bacterial biofilm. This finding was advanced by the comparison of biofilm enhancement from intact unstimulated neutrophils and from lysed or apoptotic neutrophils. Apoptotic neutrophils, with an intact cell membrane, were unable to contribute to biofilm enhancement, while lysed neutrophils evoked a similar response to that of intact cells. Using F-actin and DNA as targets, the capacity of negatively charged poly(amino acids) to disrupt, or prevent, early biofilm formation was tested. Anionic poly(aspartic acid) effectively prevented or disrupted biofilm formation. Combination of poly(aspartic acid) with DNase resulted in a synergistic increase in biofilm disruption. These results demonstrate that the presence of dying neutrophils can facilitate the initial stages of biofilm development by low inocula of P. aeruginosa. Neutrophil F-actin represents a potential new therapeutic target for disruption of pathogenic biofilms.Keywords
This publication has 43 references indexed in Scilit:
- Azithromycin Blocks Quorum Sensing and Alginate Polymer Formation and Increases the Sensitivity to Serum and Stationary-Growth-Phase Killing ofPseudomonas aeruginosaand Attenuates ChronicP. aeruginosaLung Infection inCftr−/−MiceAntimicrobial Agents and Chemotherapy, 2007
- Isolation of Pseudomonas aeruginosa from Open Ocean and Comparison with Freshwater, Clinical, and Animal IsolatesMicrobial Ecology, 2007
- Anionic poly(amino acid)s dissolve F-actin and DNA bundles, enhance DNase activity, and reduce the viscosity of cystic fibrosis sputumAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2005
- Azithromycin Retards Pseudomonas aeruginosa Biofilm FormationJournal of Clinical Microbiology, 2004
- Biofilm formation by Pseudomonas aeruginosa wild type, flagella and type IV pili mutantsMolecular Microbiology, 2003
- Whole-Genome Sequence Variation among Multiple Isolates of Pseudomonas aeruginosaJournal of Bacteriology, 2003
- Dornase alfa in early cystic fibrosis lung diseasePediatric Pulmonology, 2002
- Pseudomonas aeruginosa and other predictors of mortality and morbidity in young children with cystic fibrosisPediatric Pulmonology, 2002
- Pseudomonas biofilm formation and antibiotic resistance are linked to phenotypic variationNature, 2002
- Extracellular DNA Required for Bacterial Biofilm FormationScience, 2002