AUTHOR=Ravichandran Vinothkannan , Zhong Lin , Wang Hailong , Yu Guangle , Zhang Youming , Li Aiying 

TITLE=Virtual Screening and Biomolecular Interactions of CviR-Based Quorum Sensing Inhibitors Against Chromobacterium violaceum

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.2018.00292

DOI=10.3389/fcimb.2018.00292

ISSN=2235-2988

ABSTRACT=The rise of multi drug resistance become a global threat to the mankind. Alternate strategies have to be identified in order to fight against ‘super bugs’. Quorum sensing (QS), a cell-to-cell communication mechanism by which many bacteria regulate their biofilm and virulence factors to exert the pathogenesis. Hence, interfering the quorum sensing is found to be a novel strategy against various pathogens. Here, we intend to find out a potential CviR-mediated quorum sensing inhibitors (QSIs) against Chromobacterium violaceum. To achieve this, we have performed virtual screening from a natural products database, in vitro biofilm and violacein quantification assays. QSIs ability to curb the biofilm formation was investigated using confocal microscopy and qRT-PCR studies was employed to effect of QSI on QS regulated genes in C. violaceum. Further, to study the biomolecular interaction of CviR with QSIs, we have performed microscale thermophoresis (MST) analysis. Results suggest that SPL, BN1, BN2 and C7X have potential GScore when compared to cognate ligand and reduced the biofilm formation and violacein production significantly. Especially, BN1 drastically reduced the biofilm formation about 82.61% when supplied with 100µM. qRT-PCR studies revealed that cviI, cviR, vioB, vioC, vioD genes were significantly downregulated by QSIs. MST analysis confirmed the molecular interactions of QSIs with purified CviR protein which coheres with the docking results. Interestingly, we found that BN2 have better interaction with CviR (Kd = 45.07 ±1.90 nm). Overall results suggested that QSIs can potentially interact with CviR and inhibit the QS in a dose dependent manner. Since, LuxR homologues present in more than 100 bacterial spices, these QSIs may be developed as broad spectrum anti-infective drugs