Macrolide treatment inhibits Pseudomonas aeruginosa quorum sensing in non-cystic fibrosis bronchiectasis. An analysis from the bronchiectasis and low-dose erythromycin study trial

Burr, Lucy D., Rogers, Geraint B., Chen, Alice C.-H., Hamilton, Brett R., Pool, Gertruida F., Taylor, Steven L., Venter, Deon, Bowler, Simon D., Biga, Sally and McGuckin, Michael A. (2016) Macrolide treatment inhibits Pseudomonas aeruginosa quorum sensing in non-cystic fibrosis bronchiectasis. An analysis from the bronchiectasis and low-dose erythromycin study trial. Annals of the American Thoracic Society, 13 10: 1697-1703. doi:10.1513/AnnalsATS.201601-044OC


Author Burr, Lucy D.
Rogers, Geraint B.
Chen, Alice C.-H.
Hamilton, Brett R.
Pool, Gertruida F.
Taylor, Steven L.
Venter, Deon
Bowler, Simon D.
Biga, Sally
McGuckin, Michael A.
Title Macrolide treatment inhibits Pseudomonas aeruginosa quorum sensing in non-cystic fibrosis bronchiectasis. An analysis from the bronchiectasis and low-dose erythromycin study trial
Journal name Annals of the American Thoracic Society   Check publisher's open access policy
ISSN 2325-6621
2329-6933
Publication date 2016-10-01
Year available 2016
Sub-type Article (original research)
DOI 10.1513/AnnalsATS.201601-044OC
Open Access Status Not yet assessed
Volume 13
Issue 10
Start page 1697
End page 1703
Total pages 7
Place of publication New York, NY, United States
Publisher American Thoracic Society
Language eng
Subject 2700 Medicine
2740 Pulmonary and Respiratory Medicine
Abstract Rationale: The mechanism by which low-dose macrolide therapy reduces exacerbations in non-cystic fibrosis bronchiectasis is not known. Pseudomonas aeruginosa quorum sensing controls the expression of a range of pathogenicity traits and is inhibited by macrolide in vitro. Quorum sensing inhibition renders P. aeruginosa less pathogenic, potentially reducing its contribution to airway damage. Objectives: The aim of this study was to determine whether longterm low-dose erythromycin inhibits P. aeruginosa quorum sensing within the airways of patients with non-cystic fibrosis bronchiectasis. Methods: Analysis was performed on induced sputum from P. aeruginosa-positive subjects at recruitment to the BLESS (Bronchiectasis and Low-Dose Erythromycin Study) trial and after 48 weeks of treatment with erythromycin or placebo. To avoid changes in gene expression during culture, bacterial mRNA was extracted directly from sputum, and the relative expression of functionally critical quorum sensing genes was determined by quantitative polymerase chain reaction. Measurements and Main Results: In keeping with the BLESS study, a significant reduction in total exacerbations was seen in this subgroup (placebo: 6, [interquartile range (IQR), 4-8]; erythromycin: 3, [IQR, 3-4]; P = 0.008; Mann-Whitney test). Erythromycin therapy did not change P. aeruginosa bacterial load determined by polymerase chain reaction. A significant reduction was observed in the expression of the quorum sensing genes, lasR (erythromycin: fold change, 0.065 [IQR, 0.01-0.85], n = 11; placebo: fold change, 1.000 [IQR, 0.05-3.05]; P = 0.047,Mann-Whitney U test) and pqsA (erythromycin: fold change, 0.07 [IQR, 0.02-0.25]; placebo: fold change, 1.000 [IQR, 0.21-4.31], P = 0.017,Mann-WhitneyUtest), after 48 weeks of erythromycin, compared with placebo. Conclusions: We demonstrate inhibition of P. aeruginosa quorum sensing within the airways of patients with non-cystic fibrosis bronchiectasis receiving long-term, low-dose erythromycin, without a reduction in bacterial load, representing a potential mechanism of therapeutic impact beyond a classical antimicrobial or antiinflammatory pathway.
Formatted abstract
Rationale: The mechanism by which low-dose macrolide therapy reduces exacerbations in non-cystic fibrosis bronchiectasis is not known. Pseudomonas aeruginosa quorum sensing controls the expression of a range of pathogenicity traits and is inhibited by macrolide in vitro. Quorum sensing inhibition renders P. aeruginosa less pathogenic, potentially reducing its contribution to airway damage.

Objectives: The aim of this study was to determine whether longterm low-dose erythromycin inhibits P. aeruginosa quorum sensing within the airways of patients with non-cystic fibrosis bronchiectasis.

Methods: Analysis was performed on induced sputum from P. aeruginosa-positive subjects at recruitment to the BLESS (Bronchiectasis and Low-Dose Erythromycin Study) trial and after 48 weeks of treatment with erythromycin or placebo. To avoid changes in gene expression during culture, bacterial mRNA was extracted directly from sputum, and the relative expression of functionally critical quorum sensing genes was determined by quantitative polymerase chain reaction.

Measurements and Main Results: In keeping with the BLESS study, a significant reduction in total exacerbations was seen in this subgroup (placebo: 6, [interquartile range (IQR), 4-8]; erythromycin: 3, [IQR, 3-4]; P = 0.008; Mann-Whitney test). Erythromycin therapy did not change P. aeruginosa bacterial load determined by polymerase chain reaction. A significant reduction was observed in the expression of the quorum sensing genes, lasR (erythromycin: fold change, 0.065 [IQR, 0.01-0.85], n = 11; placebo: fold change, 1.000 [IQR, 0.05-3.05]; P = 0.047,Mann-Whitney U test) and pqsA (erythromycin: fold change, 0.07 [IQR, 0.02-0.25]; placebo: fold change, 1.000 [IQR, 0.21-4.31], P = 0.017, Mann-Whitney test), after 48 weeks of erythromycin, compared with placebo.

Conclusions: We demonstrate inhibition of P. aeruginosa quorum sensing within the airways of patients with non-cystic fibrosis bronchiectasis receiving long-term, low-dose erythromycin, without a reduction in bacterial load, representing a potential mechanism of therapeutic impact beyond a classical antimicrobial or antiinflammatory pathway.
Keyword Psuedomonas aeruginosa
Bronchiectasis
Quorum sensing
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ
Additional Notes Burr, Chen, Hamilton, Pool, Taylor, Venter, Bowler, Biga, McGuckin MRI-UQ affilated

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
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Created: Thu, 10 Nov 2016, 21:53:14 EST by Julia McCabe on behalf of Learning and Research Services (UQ Library)