For several years, mice have been used as a model for investigating the properties of pathogens. Salmonella enterica serovar Typhi (S. Typhi), is known to cause Typhoid fever in humans which in some third world countries causes many deaths annually due to poor hygiene standards. S. Typhi-murium causes the same typhoid like symptoms in mice as S. Typhi does in humans. In both mice and humans, the gastro-intestinal tract is host to the microbiota that serves as protection against bac-terial pathogens like S. Typhi and S. Typhimurium. It has previously been discovered, that strains of S. Typhimurium can overcome the colonization resistance and serve as an extremely infectious path-ogen. In an earlier experiment, a variant of S. Typhimurium with a superior ability to colonize mouse intestines has been isolated. This clone has a SNP in kdgR, which is a metabolic regulator, affecting the ED-pathway and has shown to efficiently overcome the colonization resistance. The specific mechanisms behind this are yet to be discovered. During this project, mice with the genetic compo-sition Nramp1+/+ and Nramp1-/- respectively, were infected with an equal dose of S. Typhimurium wt and the kdgR-SNP strains. The ratio between clones were determined using PCR. This allowed a full assessment of the success rate of colonization in the intestines for S. Typhimurium wt or kdgR-SNP. Furthermore, two replicate groups of mice with the genetic composition Nramp1+/+ and Nramp1-/- respectively, were infected with wt and kdgR-SNP, both with inactivated versions of SPI-1 and SPI-2. This was performed in order to investigate whether S. Typhimurium ability to col-onize the host is dependent on T3SS-1 and T3SS-2 and consequently its ability to create inflamma-tion. The results showed no significant correlation in the ratio of wt and kdgR-SNP among the in-fected mice. Statistical tests in terms of confidence intervals were performed and p-values >0,05 indicated that the results may have been found at random. Almost all performed tests showed p-values above 0,05. However, the p-value for the comparison of spleen samples from mice infected with wt and kdgR-SNP and mice infected with ΔSPI-wt and ΔSPI-kdgR-SNP showed that the results were due to the genetics of the mice. In mice infected with ΔSPI-wt and ΔSPI-kdgR-SNP, those with the genetic composition Nramp1-/- did not show any bacterial colonies and were therefor not infected. However, two mice with Nramp1+/+ showed presence of S. Typhimurium wt in their spleen, indicating that ΔSPI-wt managed to colonize the intestines without causing inflammation. The remaining Nramp1+/+ mice did not get infected. Overall, this indicates that S. Typhimurium ability to create inflammation is crucial in order for S. Typhimurium to colonize the host.
|Uddannelser||Medicinalbiologi, (Bachelor/kandidatuddannelse) Bachelor|
|Udgivelsesdato||26 maj 2016|
- Salmonella enterica serovar Typhimurim