Antibiofilm and Antivirulence Properties of Indoles Against Serratia marcescens

Abstract

Indole and its derivatives have been shown to interfere with the quorum sensing (QS) systems of a wide range of bacterial pathogens. While indole has been previously shown to inhibit QS in Serratia marcescens, the effects of various indole derivatives on QS, biofilm formation, and virulence of S. marcescens remain unexplored. Hence, in the present study, we investigated the effects of 51 indole derivatives on S. marcescens biofilm formation, QS, and virulence factor production. The results obtained revealed that several indole derivatives (3-indoleacetonitrile, 5-fluoroindole, 6-fluoroindole, 7-fluoroindole, 7-methylindole, 7-nitroindole, 5-iodoindole, 5-fluoro-2methylindole, 2-methylindole-3-carboxaldehyde, and 5-methylindole) dose-dependently interfered with quorum sensing (QS) and suppressed prodigiosin production, biofilm formation, swimming motility, and swarming motility. Further assays showed 6fluoroindole and 7-methylindole suppressed fimbria-mediated yeast agglutination, extracellular polymeric substance production, and secretions of virulence factors (e.g., proteases and lipases). QS assays on Chromobacterium violaceum CV026 confirmed that indole derivatives interfered with QS. The current results demonstrate the antibiofilm and antivirulence properties of indole derivatives and their potentials in applications targeting S. marcescens virulence.

Antibacterial and Antibiofilm Activities of Chloroindoles Against Vibrio parahaemolyticus

“…This is the first report assessing the biological activity of indole and its derivatives against V. parahaemolyticus and V. harveyi. Indole and its derivatives have been investigated for their antivirulence activity against biofilm-forming pathogens, such as P. aeruginos a, E. coli , S. marcescens , and S. aureus ( Lee et al, 2007 , 2013 ; Lee and Lee, 2010 ; Sethupathy et al, 2020 ). Indole is produced by more than 85 bacterial species and is considered an intercellular signaling molecule exploited by microbial communities ( Lee and Lee, 2010 ).…”

“…Previously, 7-fluoroindole abolished the swarming motility of the P. aeruginosa PA14 strain but not the swimming motility ( Lee et al, 2012a ). Recently, 5-fluoroindole, 6-fluoroindole, 5-methylindole, and 7-methyl indole reduced the swarming and swimming motilities in S. marcescens ( Sethupathy et al, 2020 ). And this study reports a direct correlation between the motility and biofilm formation with halogenated indoles in V. parahaemolyticus ( Figures 1 , 2 ).…”

“…The extracellular casein-degrading protease activities of the supernatant from V. parahaemolyticus grown in the presence or absence of indole compounds were measured using 2% w/v of azocasein ( Sethupathy et al, 2020 ). The culture was diluted (1:100) in fresh mLB supplemented with various concentrations of halogenated indoles, kept at 24 h with 250 rpm at 30°C, and centrifuged at 15,000 × g for 15 min.…”

“…Color confocal images were visualized using NIS-Elements C version 3.2 (Nikon eclipse). For each experiment, at least 10 random positions in three independent cultures were chosen for microscopic analysis ( Sethupathy et al, 2020 ).…”

“…In addition, 5-iodoindole eradicated persister and biofilm formation by Escherichia coli and Staphylococcus aureus ( Lee et al, 2016 ). Recently, the antimicrobial and antibiofilm activities of halogenated indoles were reported in Serratia marcescens and Acinetobacter baumanni ( Raorane et al, 2020 ; Sethupathy et al, 2020 ). Although, indole acts as an extracellular cue regulating gene expression and inhibiting ToxR regulon expression from modulating the virulence gene expression and biofilm formation in Vibrio cholerae ( Mueller et al, 2009 ; Howard et al, 2019 ), the biological activities of indole and its derivatives against V. parahaemolyticus needs to be investigated.…”