Indole decreases the virulence of pathogenic vibrios belonging to the Harveyi clade

Abstract

Aim: Indole is a signaling molecule secreted by over 85 species of bacteria, including several Vibrio species, and it has been reported to affect different bacterial phenotypes such as biofilm formation, motility, and virulence. In this study, we aimed at investigating the inter-strain variability of the effect of indole in 12 different strains belonging to the Harveyi clade of vibrios. Methods and Results:Indole reduced the virulence of all strains towards gnotobiotic brine shrimp larvae. The survival rate of brine shrimp larvae challenged with vibrios pretreated with indole was increased by 1.3-fold to 1.8-fold. Additionally, indole significantly decreased the biofilm formation in all of the strains, decreased the swimming motility in eight of the strains, and decreased swarming motility in five of the strains. When cultured in the presence of exogenous indole, the mRNA level of the pirA and pirB toxin genes were down-regulated to 65% and 46%, and to 62% and 55% in the AHPND-causing strains Vibrio parahaemolyticus M0904 and Vibrio campbellii S01, respectively. Conclusions: These data indicate that indole has a significant impact on the virulence of different strains belonging to the Harveyi clade of vibrios. Significance and Impact of the Study: Our results suggest that indole signaling is a valid target for the development of novel therapeutics in order to control infections caused by Harveyi clade vibrios in aquaculture. K E Y W O R D S acute hepatopancreatic necrosis disease (AHPND), biofilm, early mortality syndrome (EMS), motility, quorum sensing How to cite this article: Zhang, S., Yang, Q. & Defoirdt, T. (2022) Indole decreases the virulence of pathogenic vibrios belonging to the Harveyi clade.

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

“…In addition, halogenated indoles have been reported to have nematicidal and insecticidal potential ( 34 , 35 ). Although the antivirulence activity of indole in V. campbellii has been reported in our previous work ( 23 , 36 ), the concentration at which the best virulence-inhibitory activity occurred was also toxic to invertebrates.…”

“…Therefore, it is desirable to select antimicrobial agents with the ability to decrease biofilm formation. It has been reported before that indole inhibited biofilm formation in V. campbellii , V. harveyi , and V. parahaemolyticus at a relatively high concentration of 200 μM ( 23 ), and 6-fluoroindole can inhibit bacterial biofilm formation in S. marcescens at a concentration of 250 μM ( 33 ). Interestingly, 4-fluoroindole and 7-fluoroindole were shown to decrease biofilm formation at lower concentrations of 20 μM and 100 μM in Candida albicans and S. marcescens ( 30 , 42 ), whereas neither of them affected biofilm formation of V. campbellii in this study.…”

“…Indole and indole analogues are widespread in the natural environment, as a variety of bacteria and some plants produce large quantities of indole, which can be structurally modified by some non-indole-producing prokaryotes and eukaryotes ( 16 – 18 ). Indole is an interspecies and intercellular signal; it attends diverse aspects of bacterial physiology, such as spore formation ( 19 ), plasmid stability ( 20 ), drug resistance ( 21 , 22 ), biofilm formation ( 16 , 23 ), and virulence ( 24 , 25 ). Furthermore, indole and its aromatic heterocyclic structure are popularly used as synthetic starting points in the pharmaceutical industry ( 26 ), and some indole-based drugs are currently in clinical trials ( 27 , 28 ).…”

Indole analogues decreasing the virulence of Vibrio campbellii towards brine shrimp larvae

“…Indole is produced from tryptophan by tryptophanase (TnaA) in a large number of Gram‐positive and Gram‐negative bacterial species, including V. campbellii (Deeley & Yanofsky, 1981 ; Lee & Lee, 2010 ; Yang et al, 2017 ). It controls diverse aspects of bacterial physiology, such as spore formation (Kim et al, 2011 ), plasmid stability (Chant & Summers, 2007 ), drug resistance (Vega et al, 2012 ; Zhang et al, 2020 ), biofilm formation (Lee, Jayaraman, & Wood, 2007 ; Zhang et al, 2021 ), and virulence (Bommarius et al, 2013 ; Hirakawa et al, 2009 ). Interestingly, we previously found that indole decreases the virulence of vibrios belonging to the Harveyi clade towards gnotobiotic brine shrimp ( Artemia franciscana ) larvae and conventionally reared giant river prawn ( Macrobrachium rosenbergii ) larvae (Yang et al, 2017 ; Zhang et al, 2021 ).…”

5-Methylindole kills various bacterial pathogens and potentiates aminoglycoside against methicillin-resistant Staphylococcus aureus

“…In addition, indole also reduces E. coli biofilm formation ( Domka, Lee & Wood, 2006 ; Domka et al, 2007 ; Lee, Jayaraman & Wood, 2007 ). Moreover, indole was reported to increase the bacterial uptake of antimicrobials through an interaction with the Mtr permease ( Zhang, Yang & Defoirdt, 2022 ), and indole signaling is a valid target for the development of novel therapeutics in order to control infections caused by Harveyi clade vibrios in aquaculture ( Wu et al, 2022 ). These studies suggest that indole may benefit antibiotic treatment when combined with different antibiotics.…”