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Halogenated indoles decrease the virulence of Vibrio campbellii in a gnotobiotic brine shrimp model
Zhang, S.; Yang, Q.; Defoirdt, T. (2023). Halogenated indoles decrease the virulence of Vibrio campbellii in a gnotobiotic brine shrimp model. Microbiology Spectrum 10(5): 1-12. https://dx.doi.org/10.1128/spectrum.02689-22
In: Microbiology Spectrum. ASM Press: Washington. e-ISSN 2165-0497, meer
Peer reviewed article  

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Trefwoorden
    Artemia franciscana Kellog, 1906 [WoRMS]; Vibrio campbellii (Baumann, Baumann & Mandel, 1971) Baumann, Baumann, Bang & Woolkalis, 1981 [WoRMS]
Author keywords
    antivirulence therapy; indole signaling; quorum sensing; shrimp; virulence

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Abstract
    Indole signaling is viewed as a potential target for antivirulence therapy against antibiotic-resistant pathogens because of its link with the production of virulence factors. This study examined the antimicrobial and antivirulence properties of 44 indoles toward Vibrio campbellii. Based on the results, 17 halogenated indole analogues were selected, as they significantly improved the survival of brine shrimp larvae challenged with V. campbellii. Specifically, 6-bromoindole, 7-bromoindole, 4-fluoroindole, 5-iodoindole, and 7-iodoindole showed a high protective effect, improving the survival of brine shrimp to over 80% even at a low concentration of 10 μM. To explore the impact of selected indole analogues on bacterial virulence phenotypes, swimming motility, biofilm formation, protease activity, and hemolytic activity of V. campbellii were determined. The results showed that all of the 17 selected indole analogues decreased swimming motility at both 10 μM and 100 μM. Most of the indole analogues decreased biofilm formation at a concentration of 100 μM. In contrast, only a slightly decreased protease activity and no effect on hemolytic activity were observed at both concentrations. To our knowledge, this is the first study of the structure-activity relation of halogenated indole analogues with respect to virulence inhibition of a pathogenic bacterium in an in vivo host model system, and the results demonstrate the potential of these compounds in applications aiming at the protection of shrimp from vibriosis, a major disease in aquaculture.

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