2-Alkyl-4-quinolone quorum sensing molecules are biomarkers for culture-independent Pseudomonas aeruginosa burden in adults with cystic fibrosis

Zain, Nur Masirah M.; Webb, Karmel; Stewart, Iain; Halliday, Nigel; Barrett, David A.; Nash, Edward F.; Whitehouse, Joanna L.; Honeybourne, David; Smyth, Alan R.; Forrester, Douglas L.; Knox, Alan J.; Williams, Paul; Fogarty, Andrew; Cámara, Miguel; Bruce, Kenneth D.; Barr, Helen L.

Abstract

Introduction. Pseudomonas aeruginosa produces quorum sensing signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence factor production in the cystic fibrosis (CF) airways. Hypothesis/Gap statement. Culture can lead to condition-dependent artefacts which may limit the potential insights and applications of AQs as minimally-invasive biomarkers of bacterial load. Aim. We aimed to use culture-independent methods to explore the correlations between AQ levels and live P. aeruginosa load in adults with CF. Methodology. Seventy-five sputum samples at clinical stability and 48 paired sputum samples obtained at the beginning and end of IV antibiotics for a pulmonary exacerbation in adults with CF were processed using a viable cell separation technique followed by quantitative P. aeruginosa polymerase chain reaction (qPCR). Live P. aeruginosa qPCR load was compared with the concentrations of three AQs (HHQ, NHQ and HQNO) detected in sputum, plasma and urine. Results. At clinical stability and the beginning of IV antibiotics for pulmonary exacerbation, HHQ, NHQ and HQNO measured in sputum, plasma and urine were consistently positively correlated with live P. aeruginosa qPCR load in sputum, compared to culture. Following systemic antibiotics live P. aeruginosa qPCR load decreased significantly (P

Citation

Zain, N. M. M., Webb, K., Stewart, I., Halliday, N., Barrett, D. A., Nash, E. F., Whitehouse, J. L., Honeybourne, D., Smyth, A. R., Forrester, D. L., Knox, A. J., Williams, P., Fogarty, A., Cámara, M., Bruce, K. D., & Barr, H. L. (2021). 2-Alkyl-4-quinolone quorum sensing molecules are biomarkers for culture-independent Pseudomonas aeruginosa burden in adults with cystic fibrosis. Journal of Medical Microbiology, 70(10), https://doi.org/10.1099/jmm.0.001420

• Journal Article Type: Article
• Acceptance Date: Aug 10, 2021
• Online Publication Date: Oct 1, 2021
• Publication Date: Oct 1, 2021
• Deposit Date: Apr 21, 2023
• Publicly Available Date: Jun 5, 2023
• Journal: Journal of Medical Microbiology
• Print ISSN: 0022-2615
• Electronic ISSN: 1473-5644
• Publisher: Microbiology Society
• Peer Reviewed: Peer Reviewed
• Volume: 70
• Issue: 10
• DOI: https://doi.org/10.1099/jmm.0.001420
• Keywords: Microbiology (medical); General Medicine; Microbiology
• Public URL: https://nottingham-repository.worktribe.com/output/6614430
• Publisher URL: https://www.microbiologyresearch.org/content/journal/jmm/10.1099/jmm.0.001420