Attenuation of Multiple Vibrio parahaemolyticus Virulence Factors by Citral.

Yi Sun,Chao Shi,Huihui Sun,Xiaodong Xia,Zhanwen Zheng,Zi Hua,Du Guo

doi:10.3389/fmicb.2019.00894

Abstract

Citral was known as a widely used food additive with antimicrobial activity; however, whether it can be a potential therapy for controlling bacterial virulence with less risk of antimicrobial resistance remains to be investigated. Herein, we demonstrated that Vibrio parahaemolyticus virulence factors that contribute to infection were effectively inhibited to different degrees by sub-inhibitory concentrations (3.125, 6.25, and 12.5 μg/ml) of citral. Citral exerted strong inhibition of autoinducer-2 production and adhesion to Caco-2 cells. Biofilm formation of V. parahaemolyticus was effectively decreased by citral at 30°C and 20°C. Moreover, citral repressed the transcription of genes related to flagella biosynthesis, biofilm formation, type III secretion effectors, and antibiotic resistance, as well as genes contributing to the regulation of quorum sensing and toxin production. Therefore, citral could effectively attenuate multiple virulence properties of V. parahaemolyticus, and its effect on in vivo infection by V. parahaemolyticus needs further investigation.

Highlights

The increasing occurrence of disease outbreaks caused by antibiotic-resistant pathogens is becoming a major cause of mortality worldwide (Letchumanan et al, 2015)
The growth of V. parahaemolyticus was suppressed at concentrations of citral above 12.5 μg/ml (Figure 1A)
Bars represent the standard deviation (n = 3). **p ≤ 0.01. This investigation indicated that citral attenuated multiple virulence factors of V. parahaemolyticus, including quorum sensing (QS), motility, biofilm formation, the adhesion to Caco-2 cells, and repressed the expression of genes related to flagella, biofilm and T3SS1 effectors, virulence regulators, and antimicrobial peptide (AMP) resistance

Summary

Introduction

The increasing occurrence of disease outbreaks caused by antibiotic-resistant pathogens is becoming a major cause of mortality worldwide (Letchumanan et al, 2015). Anti-virulence therapies aim to inhibit the specific functions of pathogens that are required to cause infection (Rasko and Sperandio, 2010). As virulence factors are not necessary for bacterial survival, anti-virulence therapies tend to be less prone to the development of resistance and have less impact on neutral and beneficial host bacteria compared with traditional antimicrobials (Rasko and Sperandio, 2010). V. parahaemolyticus contains various virulence factors responsible for several distinct diseases, including wound infections, human acute gastroenteritis, septicemia, and even death and is a significant cause for concern regarding seafood safety (Yeung et al, 2002)

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