Date of Completion

5-4-2017

Embargo Period

5-4-2017

Keywords

Vibrio cholerae, ZInc, Selenium, Manganese, cholera toxin, motility, adhesion, GM-1 receptor, irrigation water, ex vivo adhesion

Major Advisor

Kumar Venkitanarayanan

Associate Advisor

Cameron Faustman

Associate Advisor

Mary Anne Amalaradjou

Associate Advisor

Pradeep Vasudevan

Associate Advisor

Dennis D'Amico

Field of Study

Animal Science

Degree

Doctor of Philosophy

Open Access

Campus Access

Abstract

Vibrio cholerae is a waterborne pathogen that causes human cholera. The first pandemic of cholera began in 1817 in South-east Asia, and subsequently spread to other parts of the world. Vibrio cholerae transmission to humans is through oral-fecal route. The symptoms of cholera include severe diarrhea and life-threatening dehydration. The first line of treatment against cholera is the administration of oral rehydration solution (ORS) for replenishing lost fluids. Vaccines are also given, but are considered ineffective in preventing cholera by the WHO. The third treatment option is the use of antibiotics, however, the emergence of antibiotic resistant strains of V. cholerae has triggered the search for novel approaches for controlling the infection. In this dissertation, the efficacy of three essential minerals, namely zinc, selenium and manganese was investigated for controlling V. cholerae. Specifically, the effect of three aforementioned minerals in reducing V. cholerae biofilms on polystyrene and polyvinyl chloride matrices was investigated. In addition, the efficacy of minerals in reducing V. cholerae in sewage-contaminated irrigation water was studied. The potential of zinc, selenium, and manganese for attenuating the major virulence factors in V. cholerae in vitro was determined. Finally, the efficacy of three minerals in attenuating V. cholerae virulence was validated using an ex vivo mouse intestine model and an in vivo nematode model utilizing Caenorhabditis elegans.

Results revealed that zinc and manganese effectively inhibited biofilm synthesis and inactivated mature biofilms of V. cholerae on polystyrene and PVC. Moreover, the three minerals significantly decreased viable V. cholerae counts in irrigation water. At respective sub-inhibitory concentration, the three essential minerals significantly decreased V. cholerae motility and adhesion to intestinal epithelial cells, and cholera toxin production. These results were confirmed by ex vivo and in vivo models, where the minerals decreased V. cholerae colonization and toxin production in mouse intestine, and enhanced the survival of V. cholerae-infected C. elegans. Collectively, the above results highlight the potential use of zinc, selenium and manganese for controlling V. cholerae.

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