Antibacterial and Antibiofilm Activities of Chloroindoles Against Vibrio parahaemolyticus

Abstract

Vibrio parahaemolyticus is a food-borne pathogen recognized as the prominent cause of seafood-borne gastroenteritis globally, necessitating novel therapeutic strategies. This study examined the antimicrobial and antivirulence properties of indole and 16 halogenated indoles on V. parahaemolyticus. Among them, 4-chloroindole, 7-chloroindole, 4-iodoindole, and 7-iodoindole effectively inhibited planktonic cell growth, biofilm formation, bacterial motility, fimbrial activity, hydrophobicity, protease activity, and indole production. Specifically, 4-chloroindole at 20 μg/mL inhibited more than 80% of biofilm formation with a minimum inhibitory concentration (MIC) of 50 μg/mL against V. parahaemolyticus and Vibrio harveyi. In contrast, 7-chloroindole inhibited biofilm formation without affecting planktonic cell growth with a MIC of 200 μg/mL. Both chlorinated indoles caused visible damage to the cell membrane, and 4-chloroindole at 100 μg/mL had a bactericidal effect on V. parahaemolyticus within 30 min treatment, which is superior to the effect of tetracycline at the same dose. The quantitative structure-activity relationship (QSAR) analyses revealed that chloro and bromo at positions 4 or 5 of the indole are essential for eradicating the growth of V. parahaemolyticus. These results suggest that halogenated indoles have potential use in antimicrobial and antivirulence strategies against Vibrio species.

The Anticancer Agent 3,3'-Diindolylmethane Inhibits Multispecies Biofilm Formation by Acne-Causing Bacteria and Candida albicans

“…Several indole derivatives have been shown to exhibit antibiofilm activity against various microbes, for example, 3-indolylacetonitrile against enterohemorrhagic E. coli O157:H7 (14), methylindoles ( 18 ) or 7‐benzyloxyindole ( 27 ) against C. albicans , iodoindoles against A. baumannii ( 19 ), several halogenated indoles derivatives against S. marcescens ( 20 ), and chloroindoles against V. parahaemolyticus ( 21 ). Unlike other indoles in previous studies, in this study, DIM and indole-3-carbinol both efficiently inhibited biofilm formation by C. acnes .…”

“…In particular, indole controls quorum sensing and biofilm formation of its own species and in other bacterial species ( 12 ). However, several indole derivatives have more potent antimicrobial and antibiofilm activities than indole such as 3-indolylacetonitrile, 7-hydroxyindole, 7-benzyloxyindole, methylindoles, iodoindoles, fluoroindoles, chloroindoles against Escherichia coli ( 14 , 15 ), Pseudomonas aeruginosa ( 15 ), Paenibacillus alvei ( 16 ), S. aureus ( 17 ), C. albicans ( 18 ), Acinetobacter baumannii ( 19 ), Serratia marcescens ( 20 ), Vibrio parahaemolyticus ( 21 ), and others.…”

Anti-Biofilm and Antibacterial Activities of Cycas media R. Br Secondary Metabolites: In Silico, In Vitro, and In Vivo Approaches

“…Interestingly, some antibiotics can affect bacterial virulence in addition to their growth inhibition ability. For instance, it was reported that linezolid could diminish the virulence factors’ production from S. aureus [ 50 , 51 ]. Thus, we also explored the anti-biofilm activity of SOTE by crystal violet assay and qRT-PCR.…”

“…Antimicrobial compounds are usually more effective when they also have anti-biofilm activity. They will be able to penetrate the formed biofilms, exert their antibacterial activity, and diminish biofilm formation [ 51 ]. SOTE decreased the percentage of E. faecalis isolates strongly and moderately, forming biofilm from 60.87% to 21.74%.…”

Halogenated Indoles Decrease the Virulence of Vibrio campbellii in a Gnotobiotic Brine Shrimp Model

“…Recently, several indole analogues have been reported to reduce bacterial virulence. For example, 4-iodoindole, 7-iodoindole, 4-chloroindole, and 7-chloroindole were found to effectively inhibit biofilm formation, bacterial motility, fimbrial activity, hydrophobicity, protease activity, and indole production in Vibrio parahaemolyticus ( 29 ). Furthermore, 7-fluoroindole ( 30 ), 7-hydroxyindole ( 31 ), and 3-indolylacetonitrile ( 32 ) reduced the production of virulence factors in Pseudomonas aeruginosa .…”