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-2-methylindole, 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 6-fluoroindole 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.
Highlights
Serratia marcescens is a Gram-negative, rod-shaped bacterium that belongs to the Enterobacteriaceae family and well-known for its ability to produce prodigiosin a red pigment (Williamson et al, 2006)
The quorum sensing inhibitory activities of the 51 indole derivatives were assessed by measuring their abilities to inhibit prodigiosin production by S. marcescens
These results indicate indoles effectively suppress prodigiosin synthesis and biofilm formation by S. marcescens by inhibiting quorum sensing (QS) activity rather than by exhibiting antimicrobial activity, which suggests indoles may be less prone to the development of drug resistance than conventional antibiotics
Summary
Serratia marcescens is a Gram-negative, rod-shaped bacterium that belongs to the Enterobacteriaceae family and well-known for its ability to produce prodigiosin a red pigment (Williamson et al, 2006). Antibiofilm and Antivirulence Potentials of Indoles are caused by Serratia spp. in the United States and Europe (Sader et al, 2014). Serratia spp. is known to be the 7th and 10th most common cause of pneumonia and bloodstream infections, respectively, in United States and Europe (Acar and Goldstein, 1997; Jones, 2010). S. marcescens isolates of clinical origin have been shown to produce extended-spectrumβ-lactamase (Yang et al, 2012), and to acquire multiple drug resistance via horizontal gene transfer from other members of the Enterobacteriaceae family (Ivanova et al, 2008). The bacterium is known to utilize a broad array of nutrients and to grow in the presence of antiseptics, detergents, and disinfectants (Cooney et al, 2014)
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