Abstract
BackgroundBurgeoning antibiotic resistance in Pseudomonas aeruginosa has necessitated the development of anti pathogenic agents that can quench acylhomoserine lactone (AHL) mediated QS with least risk of resistance. This study explores the anti quorum sensing potential of T. chebula Retz. and identification of probable compounds(s) showing anti QS activity and the mechanism of attenuation of P. aeruginosa PAO1 virulence factors.Methods and ResultsMethanol extract of T. chebula Retz. fruit showed anti QS activity using Agrobacterium tumefaciens A136. Bioactive fraction (F7), obtained by fractionation of methanol extract using Sephadex LH20, showed significant reduction (p<0.001) in QS regulated production of extracellular virulence factors in P. aeruginosa PAO1. Biofilm formation and alginate were significantly (p<0.05) reduced with enhanced (20%) susceptibility to tobramycin. Real Time PCR of F7 treated P. aeruginosa showed down regulation of autoinducer synthase (lasI and rhlI) and their cognate receptor (lasR and rhlR) genes by 89, 90, 90 and 93%, respectively. Electrospray Ionization Mass Spectrometry also showed 90 and 64% reduction in the production of 3-oxo-C12HSL and C4HSL after treatment. Decrease in AHLs as one of the mechanisms of quorum quenching by F7 was supported by the reversal of inhibited swarming motility in F7-treated P. aeruginosa PAO1 on addition of C4HSL. F7 also showed antagonistic activity against 3-oxo-C12HSL-dependent QS in E. coli bioreporter. C. elegans fed on F7-treated P. aeruginosa showed enhanced survival with LT50 increasing from 24 to 72 h. LC-ESI-MS of F7 revealed the presence of ellagic acid derivatives responsible for anti QS activity in T. chebula extract.ConclusionsThis is the first report on anti QS activity of T. chebula fruit linked to EADs which down regulate the expression of lasIR and rhlIR genes with concomitant decrease in AHLs in P. aeruginosa PAO1 causing attenuation of its virulence factors and enhanced sensitivity of its biofilm towards tobramycin.
Highlights
This is the first report on anti QS activity of T. chebula fruit linked to ellagic acid derivatives (EADs) which down regulate the expression of lasIR and rhlIR genes with concomitant decrease in acylhomoserine lactone (AHL) in P. aeruginosa PAO1 causing attenuation of its virulence factors and enhanced sensitivity of its biofilm towards tobramycin
P. aeruginosa is the major cause of secondary infections in immunocompromised patients with cystic fibrosis, burn wound and HIV causing maximum morbidity and mortality [1]
This study explores the anti QS potential of T. chebula fruit for attenuation of virulence factors of P. aeruginosa PAO1 and identification of compounds (s) responsible for the activity
Summary
P. aeruginosa is the major cause of secondary infections in immunocompromised patients with cystic fibrosis, burn wound and HIV causing maximum morbidity and mortality [1]. It is a clinically important opportunistic pathogen responsible for 57% of total nosocomial infections [2]. To facilitate the establishment of infection, P. aeruginosa produces both cell-associated and extracellular virulence factors globally regulated by well defined quorum sensing systems arranged in hierarchical manner with las system at the top, positively controlling the activity of rhl system [3]. The las system utilizes N-(3-oxododecanoyl)-L-homoserine lactone (3-oxoC12HSL) whereas rhl system functions by means of N-butanoyl-Lhomoserine lactone (C4HSL) as the signal molecules [4]. This study explores the anti quorum sensing potential of T. chebula Retz. and identification of probable compounds(s) showing anti QS activity and the mechanism of attenuation of P. aeruginosa PAO1 virulence factors
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
