Virulence regulation of enteropathogenic bacteria by capsaicin-rich natural products, exploring Cytolethal Distending Toxin and Quorum Sensing molecules

The true pathophysiology of Irritable Bowel Syndrome (IBS) remains unknown, but an increasingly recognised hypothesis is the development of IBS following an episode of acute gastroenteritis [post-infectious (PI)-IBS] (1). Enteropathogenic Escherichia coli and Campylobacter jejuni cause PI-IBS. Among many, two are the bacterial key factors that induce PI-IBS: production of exo-toxins, as Cytolethal Distending Toxin that destroys host’s cells, and possession of Multi-Drug Resistance (MDR) traits that turn inefficient many synthetic antimicrobials. To contrast similar pathogens when antibiotics fail, the therapeutic use of natural products is often successful. However, the knowledge on the molecular biology underlying the bioactivity of natural products on bacterial cells is still little. Since LuxS expression induces virulence, and Hns and Dksa reduce virulence, we hypothesize that down-regulation of Cdt-B goes with down-regulation of LuxS and up-regulation of Hns and DksA. Our results show that Capsicum extracts down-regulate Cdt-B expression (up to 60 folds in E. coli and 40 folds in C. jejuni), down-regulate LuxS (up to 24 folds in E. coli and 14 folds in C. jejuni), and up-regulate Hns and Dksa (up to 15 folds in E. coli and 9 folds in C. jejuni), in comparison to untreated samples.Capsicum extracts are able to reduce the pathogenicity of bacteria causing PI-IBS, likewise antibiotics. The attenuation of CDT that we obtained is not as a random gene silencing, but is backed by the down-regulation of Quorum Sensing Autoinducer-2 and by the up-regulation of Transcriptional regulators. The need to find alternatives to synthetic antimicrobials in order to control human pathogens is impellent, because the ability of bacteria to overcome the obstacle of synthetic drugs is rapidly increasing .