AUTHOR=Husain Fohad Mabood , Ahmad Iqbal , Khan Faez Iqbal , Al-Shabib Nasser A. , Baig Mohammad Hassan , Hussain Afzal , Rehman Md Tabish , Alajmi Mohamed F. , Lobb Kevin A. 

TITLE=Seed Extract of Psoralea corylifolia and Its Constituent Bakuchiol Impairs AHL-Based Quorum Sensing and Biofilm Formation in Food- and Human-Related Pathogens

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=Volume 8 - 2018

YEAR=2018

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2018.00351

DOI=10.3389/fcimb.2018.00351

ISSN=2235-2988

ABSTRACT=Emergence of multi-drug resistance in pathogenic bacteria in clinical settings as well as food-borne infections has become a serious health concern. Problem of drug resistance necessitates the need for alternative novel therapeutic strategy to combat this menace. One such approach is targeting the quorum-sensing (QS) controlled virulence and biofilm formation. In this study, we firstly screened different fractions of Psoralea corylifolia (seed) for their anti-QS property in C. violaceum 12472 strain. Methanol fraction was found to be the most active fractions and was selected for assays. At sub-inhibitory concentration P. corylifolia methanol fraction (PCMF) reduced QS regulated virulence functions in C. violaceum CVO26 (violacein); P. aeruginosa (elastase, protease, pyocyanin, chitinase, EPS and swarming motility), A. hyrophila (protease, EPS) and S. marcescens (prodigiosin). Biofilm formation in all the test pathogens was reduced significantly (p ≤ 0.005) in a concentration dependent manner. β-galactosidase assays showed that PCMF at 1000 µg/ml down-regulated las-controlled transcription in PAO1. In vivo studies with C. elegans demonstrated increased survival of the nematode after treatment with PCMF. Bakuchiol, a phytoconstituent of the extract demonstrated significant inhibition of QS regulated violacein production in C. violaceum and impaired the biofilm formation in the test pathogens. Docking studies suggested that bakuchiol effectively binds to the active site cavity of LasR and RhlR, and the complexes are stabilized by several interactions. Further, molecular dynamics simulation of LasR, LasR-bakuchiol, RhlR, and RhlR-bakuchiol complex under explicit water condition for 50 ns revealed that binding of bakuchiol to LasR and RhlR was quite stable. The study highlights the anti-infective potential of PCMF and bakuchiol as instead of bactericidal or bacteriostatic action, the extract targets QS controlled virulence and biofilm.