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To study co-operative co-infection in pathogenic Vibrio cholera and its impact on cholera outbreaks

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Cholera, caused by the bacterium Vibrio cholerae, is a worldwide public health concern with over 100,000 deaths reported every year mainly in small children. Even small amounts of detectable cholera bacteria in drinking water can lead outbreaks although in laboratory experiments large numbers of V. cholerae are typically needed to cause disease. In our experiments, we will address this discrepancy by analyzing factors that make the infection with small numbers of bacteria more likely. Understanding the regulation of infectivity and why small doses of V. cholerae can cause disease will improve our understanding of the fundamental mechanisms of bacterial infection and may help mitigate outbreaks in the future.
Animal models are necessary for this study since it is not possible to replicate all aspects of bacterial colonization and infection in an artificial system. The infant mouse model is well established and mimics key colonization features of humans but without fatal diarrhea and significantly less distress to animals. In our planned experiments, we will use 1430 CD-1 mice during the duration of ~2 years to address our hypothesis. Using our novel STAMP technology we are able to greatly reduce the number of animals needed by a factor of approximately 500-fold to investigate colonization population dynamics with similar accuracy. This is due to the greatly increased precision of our measurements and the ability to track multiple factors simultaneously, which reduces the total size needed to see a difference and the number of experiments which need to be performed.