Role of Quorum Sensing in Pseudomonas aeruginosa Adaptations During Chronic Obstructive Pulmonary Disease

Abstract

Chronic obstructive pulmonary disease (COPD) is abrupt exacerbation of the respiratory system which continues for prolonged days which lead to pneumonia resulting from failure to eradicate bacterial infections and are responsible for a tremendous burden of hospitalizations and deaths. Pseudomonas aeruginosa makes the major contribution in worsening the condition by employing virulence and biofilm mode of life style in order to survive in the competitive environment and repeated exposure to antibiotics. Thus, an idea was put forward to suppress the virulence and biofilm formation by the novel therapeutic approaches. P. aeruginosa secretes virulence factors which are controlled by a density dependent mechanism known as quorum sensing. Introduction of the novel quorum sensing molecules would be promising target and to surpass the antibiotic resistant. We have isolated 21 P. aeruginosa clinical strains from 96 sputum of patients of COPD, which were identified by 16S rRNA sequencing analysis. Furthermore, different virulence aspects responsible for pathogenicity rendered on the host such as, pyocyanin, siderophore, elastase, biofilm, exopolysaccharides, motility features, AHL production were assessed. Quorum sensing regulated gene expression analysis was carried out to understand differential expression of las and rhl in regulating quorum sensing mechanism. Most of the clinical strains were rich producers of the biofilm and virulence factors as compared with the control P. aeruginosa PAO1. As the part of the intervention strategy, 6 Methycloumarin (6MC) and 7 Ethoxycoumarin (7EC) as novel quorum sensing inhibiting molecule were introduced, which is successful in reducing the various virulence factors secreted by P. aeruginosa, significantly (p lt 0.001) at 125 and#956;g/mL. C. elegans based survival assay was carried with the help of 6MC and 7EC as therapeutic intervention, which saved the worms from the infection of P. aeruginosa. Efficient biocompatibility nature was seen for compounds as revealed by MTT and acridine orange