AUTHOR=Saha Subhasree , Aggarwal Shifu , Singh Durg Vijai 

TITLE=Attenuation of quorum sensing system and virulence in Vibrio cholerae by phytomolecules

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1133569

DOI=10.3389/fmicb.2023.1133569

ISSN=1664-302X

ABSTRACT=<p>The <italic>Vibrio cholerae,</italic> a gram-negative bacterium, is the causative agent of cholera. Quorum sensing is a cell-to-cell communication that leads to gene expression, accumulation of signaling molecules, biofilm formation, and production of virulence factors. The quorum sensing pathway in <italic>V. cholerae</italic> is regulated by <italic>lux</italic>O, and biofilm formation and other virulence factors are positively controlled by <italic>aph</italic>A and negatively by <italic>hap</italic>R. Hence, targeting the global regulator <italic>lux</italic>O would be a promising approach to modulate the QS to curtail <italic>V. cholerae</italic> pathogenesis. The present study investigated the modulating activity of quercetin and naringenin on biofilm formation and quorum-sensing regulated phenotypes in <italic>V. cholerae</italic>. Then after we determined the anti-quorum sensing capability of phytomolecules against the model organism <italic>Chromobacterium violaceum</italic>. Also, we performed flow cytometry for live/dead bacteria, MTT assay, CLSM, and growth curve analysis to determine their role as QS modulators rather than anti-bacterial. <italic>V. cholerae</italic> strains VC287 and N16961 formed thick biofilm. We observed a two-fold reduction in the expression of biofilm-associated genes comprising <italic>gbpA, vpsA, rbmA</italic>, and <italic>mbaA</italic> in the presence of phytomolecules indicating that phytomolecules modulate quorum sensing pathway rather than killing the bacteria. These phytomolecules were non-toxic and non-hemolytic and had anti-adhesion and anti-invasion properties. In addition, quercetin and naringenin were found to be highly effective compared to known quorum-sensing inhibitors terrein and furanone C-30. Thus, this study provides evidence that phytomolecules: quercetin and naringenin modulate the quorum-sensing pathway rather than killing the bacteria and can be used as an anti-quorum-sensing molecule for therapy against the pathogen.</p>