The Evolution of Pathogens and the Immune Response: The host immune response to a ‘hyperinfectious’ isolate of the mouse enteropathogen Citrobacter rodentium

Abstract

Infectious diseases are one of the leading causes of death worldwide. Microbes have an amazing ability of being able to quickly adapt to their environments, sometimes causing new or worse disease in their hosts as a consequence. The Bioluminescent Superbugs Lab group have previously studied the evolution of Citrobacter rodentium bioluminescent derivative ICC180 in its natural host, the laboratory mouse. After 20 natural transmission steps, a ‘hyperinfectious’ C. rodentium strain (designated as N4) was isolated. N4 is capable of transmitting to naïve hosts faster than its ICC180 ancestor. This work aims to investigate whether the ancestral and ‘evolved’ strains elicit differential immune responses from their host. C57BL/6 mice were artificially infected by oral gavage with either ICC180 or N4. Groups of mice were then euthanized at 3, 7, 14 and 21 days post-infection and various samples were collected. I monitored the infection using biophotonic imaging and also collected stools regularly for the enumeration of bacteria. Colon sections were collected for histopathology, cytokine analysis, and analysis of neutrophil activity. Blood serum, colon and caecal washes were collected and analysed for production of antibodies to C. rodentium. It was observed that although the ‘evolved’ C. rodentium strain did not cause an increase in the severity of symptoms, it did induce a stronger inflammatory response compared to the ancestor. This immunological work has added to previous work done by our group, with a focus on the body’s own response to disease. In doing so, it has emphasised the need for in vivo models in experimental evolution studies. The work done in this thesis has laid the foundations for additional immunological studies into the current ‘evolved’ C. rodentium strain, N4, as well as other ‘evolved’ C. rodentium isolates.