Vibrio cholerae vexH Encodes a Multiple Drug Efflux Pump That Contributes to the Production of Cholera Toxin and the Toxin Co-Regulated Pilus

The resistance-nodulation-division (RND) efflux systems are ubiquitous transporters that function in antimicrobial resistance. Recent studies showed that RND systems were required for virulence factor production in Vibrio cholerae. The V. cholerae genome encodes six RND efflux systems. Three of the RND systems (VexB, VexD, and VexK) were previously shown to be redundant for in vitro resistance to bile acids and detergents. A mutant lacking the VexB, VexD, and VexK RND pumps produced wild-type levels of cholera toxin (CT) and the toxin co-regulated pilus (TCP) and was moderately attenuated for intestinal colonization. In contrast, a RND negative mutant produced significantly reduced amounts of CT and TCP and displayed a severe colonization defect. This suggested that one or more of the three uncharacterized RND efflux systems (i.e. VexF, VexH, and VexM) were required for pathogenesis. In this study, a genetic approach was used to generate a panel of V. cholerae RND efflux pump mutants in order to determine the function of VexH in antimicrobial resistance, virulence factor production, and intestinal colonization. VexH contributed to in vitro antimicrobial resistance and exhibited a broad substrate specificity that was redundant with the VexB, VexD, and VexK RND efflux pumps. These four efflux pumps were responsible for in vitro antimicrobial resistance and were required for virulence factor production and intestinal colonization. Mutation of the VexF and/or VexM efflux pumps did not affect in vitro antimicrobial resistance, but did negatively affect CT and TCP production. Collectively, our results demonstrate that the V. cholerae RND efflux pumps have redundant functions in antimicrobial resistance and virulence factor production. This suggests that the RND efflux systems contribute to V. cholerae pathogenesis by providing the bacterium with protection against antimicrobial compounds that are present in the host and by contributing to the regulated expression of virulence factors

Conceptualising challenging experiences and post-travel culture involvement

When cultural differences are significant and contact is relatively brief, it can be difficult to find personal relevance in the cultures of others, let alone develop an enduring interest in the host cultures, which would continue after travel. This chapter addresses these cultural tourism issues by examining the relationship between the concepts of challenge and post-travel culture involvement, and their association with self-development. The conceptual framework proposed here draws on interconnected theories from acculturation, cognitive appraisal and positive psychology, as well as relevant literature on immersive, memorable, adventure and transformative tourist experiences. It concludes that the acculturation process models and the stress, appraisal and coping theory are the most helpful for explaining this underlying relationship and for providing a more nuanced understanding of challenge in the context of cultural tourism