Dietary Isothiocyanates, Sulforaphane and 2-Phenethyl Isothiocyanate, Effectively Impair Vibrio cholerae Virulence

Abstract

Vibrio cholerae represents a constant threat to public health, causing widespread infections, especially in developing countries with a significant number of fatalities and serious complications every year. The standard treatment by oral rehydration does not eliminate the source of infection, while increasing antibiotic resistance among pathogenic V. cholerae strains makes the therapy difficult. Thus, we assessed the antibacterial potential of plant-derived phytoncides, isothiocyanates (ITC), against V. cholerae O365 strain. Sulforaphane (SFN) and 2-phenethyl isothiocyanate (PEITC) ability to inhibit bacterial growth was assessed. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values indicate that these compounds possess antibacterial activity and are also effective against cells growing in a biofilm. Tested ITC caused accumulation of stringent response alarmone, ppGpp, which indicates induction of the global stress response. It was accompanied by bacterial cytoplasm shrinkage, the inhibition of the DNA, and RNA synthesis as well as downregulation of the expression of virulence factors. Most importantly, ITC reduced the toxicity of V. cholerae in the in vitro assays (against Vero and HeLa cells) and in vivo, using Galleria mellonella larvae as an infection model. In conclusion, our data indicate that ITCs might be considered promising antibacterial agents in V. cholerae infections.

Sulforaphane-Enriched Extracts from Broccoli Exhibit Antimicrobial Activity against Plant Pathogens, Promising a Natural Antimicrobial Agent for Crop Protection

“…The MIC of AITC for all tested bacteria was 100 μg/mL [ 58 ]. The MIC of phenethyl isothiocyanate (PEITC), which is also prevalent in cruciferous plants, ranges from 41 to 81 μg/mL [ 15 ]. Flavonic acid BB, derived from plants, inhibits clinical S. haemolyticus strains and their biofilms.…”

“…For instance, SFN inhibits S. dysenteriae by negatively regulating the expression of Shiga toxin [ 12 ]. SFN and related compounds exhibit a strong inhibitory effect on H. pylori , a bacterium responsible for human gastritis and stomach cancer, and effectively impair the virulence of V. cholerae [ 13 , 14 , 15 ]. Available evidence in the model plant A. thaliana suggested that SFN also has antimicrobial potential against plant pathogens.…”

Evaluation of the Anti-Shigellosis Activity of Dietary Isothiocyanates in Galleria mellonella Larvae

“…The SFN action in promoting phagocytosis was widely investigated previously [43,44]. In our recent work, we have shown that this mechanism is involved in bacterial clearance in the V. cholerae infection [23]. The finding of therapeutic properties of SFN in the course of the S. dysenteriae infection of both cell lines and the animal model is a key step in developing the strategy to use the dietary phytoncides in therapy.…”

“…Nevertheless, we showed that ITC could inhibit the growth of several bacterial pathogens, including Klebsiella pneumoniae and Staphylococcus aureus. Recently, we also presented evidence for the antibacterial action of ITCs against another toxin-producing bacterium, Vibrio cholerae [23].…”