The ability of intracellular pathogens to invade and spread from non-phagocytic cell to another is an imperative mechanism broadly investigated in cellular biology. Listeria monocytogenes (Lm) –one example of intracellular pathogens, invades specifically human epithelial cells using its surface proteins Internalin A (InlA) and InlB, respectively. InlA alone is sufficient to internalise the pathogen into the host cells by interacting with human E-cadherin –specifically the N-terminal domain 1 (hEC1). The InlA variant (InlAm) that was previously made to increase the binding affinity to hEC1 was successfully engineered in this study. This variant was found to interact with N-terminal domain 1 of murine E-cadherin (mEC1) by isothermal titration calorimetry (ITC). Previously, the InlAm was reported to allow Lm invasion into M villous cells that express murine N-cadherin –possibly via the N-terminal domain 1 (mNC1). In this study, InlAm did not have affinity for mNC1 or N-terminal domain 1 of human N-cadherin (hNC1) when analysed by ITC –possibly due to amino acid sequences variation from both mEC1 and hEC1. However, by structurally engineering the complexes (InlAm/mNC1 and InlAm/hNC1) and studying their interaction interfaces, it was revealed that mNC1 and hNC1 can be recognised by InlAm just like hEC1. This was supported by the distances between interacting amino acid residues in InlAm/hEC1 crystal structure complex, which were also conserved in the engineered complexes. These observations related to the fact that the N-terminal domains of E- and N-cadherin are structurally conserved, therefore that could have attributed to similarities observed in the engineered complexes. Therefore, future studies would aim at using alternative methods that could support or disprove one of the two findings, that is whether InlAm and any of the N-terminal domains of N-cadherin interact or not. / Dissertation (MSc)--University of Pretoria, 2016. / National Research Foundation (NRF) / The Allan Gray Orbis Foundation / The Mandela Rhodes Foundation / Biochemistry / MSc / Unrestricted