Abstract
Pseudomonas aeruginosa is an ambidextrous Gram-negative contagium with density convoluted network defined quorum sensing, which enables the persistent survival within the host environment, contributing to various lung related diseases including Chronic Obstructive Pulmonary Disease (COPD). It is clear that P. aeruginosa is a powerful, exquisite pathogen that has adopted a variety of virulence properties through quorum sensing (QS) regulated phenomenon and that it dominates both in the development and exacerbations of COPD. Interestingly, 7-Ethoxycoumarin (7-EC), a compound that adequately mimics QS signaling molecule of P. aeruginosa, was introduced as part of the process of developing novel ways to treat the severe exacerbations. The results showed that, introduction of 7-EC significantly decreased exopolysaccharide-mediated biofilm development of strains isolated from COPD sputum, as evidenced by SEM analysis. Furthermore, 7-EC was able to modulate a variety of virulence factors and motility without subjecting planktonic cells to any selection pressure. Bacterial invasion assay revealed the potential activity of the 7-EC in preventing the active entry to A549 cells without causing any damage to the cells and found functionally active in protecting the C. elegans from P. aeruginosa infection and being non-toxic to the worms. Docking analysis was further proved that 7-EC to be the potential anti-QS compound competing specifically with Rhl and Pqs Systems. Therefore, 7-EC in the utilisation against the P. aeruginosa based infections, may open an avenue for the futuristic mechanistic study in chronic respiratory diseases and a initiator for the development of non-antibiotic based antibacterial therapy.
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This research was supported by DBT, New Delhi (Grant No: BT/PR41393/MED/30/2298/2020).
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SKB: Investigation, writing—original draft. AP: Methodology, writing—review and editing. YPB: Supervision, methodology, writing—review and editing. KMI: Supervision, resources, writing—review and editing. RPS: Funding acquisition, conceptualization, methodology, resources, supervision, writing—review and editing.
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11274_2023_3655_MOESM1_ESM.tif
Figure S1: Bacterial morphotypes from sputum sample (A) and phylogeny analysis (B). Gram staining of COPD sputum sample showing bacterial morphotypes under oil immersion field (×100) and the presence of P. aeruginosa was suggested by the tiny gram-negative rods (A). P. aeruginosa RS08 evolutionary relationship to its closest BLAST hits was be shown in a phylogenetic tree based on the 16S rDNA gene and generated via neighbor-joining. The MEGA-11 software was employed by 1000 boot straps to maintain the neighbor-joining tree (B). (TIF 4636 kb)
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Bajire, S.K., Prabhu, A., Bhandary, Y.P. et al. 7-Ethoxycoumarin rescued Caenorhabditis elegans from infection of COPD derived clinical isolate Pseudomonas aeruginosa through virulence and biofilm inhibition via targeting Rhl and Pqs quorum sensing systems. World J Microbiol Biotechnol 39, 208 (2023). https://doi.org/10.1007/s11274-023-03655-8
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DOI: https://doi.org/10.1007/s11274-023-03655-8