Pilot study to establish the suitable mice-model strain to study cooperative coinfection in Vibrio cholerae
Cholera is caused by Vibrio cholerae, which is a serious threat to public health with more than 100,000 deaths reported every year - mainly in children under 5 years. The pathogen is mainly spread via contaminated water. Under laboratory conditions, a large number of V. cholerae is required to cause infections. However, the number of infective bacteria in the environment is low making it unlikely that the experimentally determined infective dose is taken up in a single event. Our project aims to address this discrepancy by studying whether several small doses over a period instead of a single large infective dose can cause infection, i.e., can a first small infective dose, by itself not enough to cause disease, make the host more susceptible to subsequent doses?
Animal models are necessary for this study since it is not possible to replicate all the aspects of bacterial colonization and infection in 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. However, in CD-1 mice (that we currently use) already small doses of V. cholerae cause infections. The literature suggests that other mice strains are more resilient and therefore better suited to study if small non-infectious doses sensitize the host for subsequent doses. Unfortunately, infection conditions are varied and therefore difficult to compare. In this application, I am applying for a pilot experiment with 88 infant mice and 12 adult mice from different mouse strains to determine the infectious dose required to colonize at least 50% of the population (ID50) and select the best suited strain for my future experiments.
Animal models are necessary for this study since it is not possible to replicate all the aspects of bacterial colonization and infection in 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. However, in CD-1 mice (that we currently use) already small doses of V. cholerae cause infections. The literature suggests that other mice strains are more resilient and therefore better suited to study if small non-infectious doses sensitize the host for subsequent doses. Unfortunately, infection conditions are varied and therefore difficult to compare. In this application, I am applying for a pilot experiment with 88 infant mice and 12 adult mice from different mouse strains to determine the infectious dose required to colonize at least 50% of the population (ID50) and select the best suited strain for my future experiments.