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

Klaudyna Krause,Agnieszka Pyrczak-Felczykowska,Magdalena Narajczyk,Agnieszka Szalewska-Pałasz,Anna Herman-Antosiewicz,Dariusz Nowicki,Monika Karczewska

doi:10.3390/ijms221910187

Klaudyna Krause, Agnieszka Pyrczak-Felczykowska + Show 5 more

Open Access

https://doi.org/10.3390/ijms221910187

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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.

Highlights

Cholera infection caused by the Gram-negative, aquatic bacterium Vibrio cholerae leads to severe dehydrating diarrhea [1]
It can be expected that the imbalance between rising antimicrobial resistance among bacterial pathogens and the availability of treatment strategies will expand continuously [26,27]
In this study, we decided to employ two members of ITC group, naturally occurring in Brassicaceae plants, SFN and phenethyl isothiocyanate (PEITC), to test their antibacterial potency against V. cholerae. Their antimicrobial effect was demonstrated for such bacterial pathogens as E. coli, E. faecalis, S. aureus, Salmonella

Summary

Introduction

Cholera infection caused by the Gram-negative, aquatic bacterium Vibrio cholerae leads to severe dehydrating diarrhea [1]. The worldwide spread of V. cholerae has caused seven large pandemic events in recorded history and remains a serious threat to public health in developing countries [2,3]. 2 to 9 million cases of cholera occur annually, resulting in near 100,000 deaths [4]. The antibiotic resistance among V. cholerae strains is increasingly reported and threatens our ability to treat infected patients—which has created a major challenge to the development of an efficient therapy [5,6,7]. Oral rehydration treatment (ORT) is still the first-choice therapy for infected patients [8]. Intravenous rehydration and antibiotics are employed to reduce severe complication development. The ORT helps only to reduce symptoms of infection instead of actual treatment and cannot

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