Aim: To generate an antibody-antibiotic conjugate directed against Burkholderia pseudomallei and to investigate combinational therapies. This involves antibody, antibiotics and autophagy promoting compounds as potential alternative therapies for melioidosis. Melioidosis is a severely neglected tropical disease caused by the gram negative bacterium B. pseudomallei. The bacterium can subvert the host immune system and form an intracellular niche protected from current antibiotic therapies. This project aims to investigate monoclonal antibodies and novel antimicrobial compounds as potential therapeutics for melioidosis. An antibody will be incorporated into an antibody-antibiotic conjugate (AAC) which has the potential to specifically target bacteria and localise delivery of antibiotics to the site of intracellular infection. RAW 264.7 macrophage-like cell infection assays have been used to down select monoclonal antibodies based on their ability to opsonise Burkholderia in vitro. Imaging flow cytometry and colony count data has shown that antibodies directed against the capsule polysaccharide (CPS) of Burkholderia are opsonising and significantly increase bacterial uptake into RAW cells. Confocal microscopy data shows that antibody opsonised bacteria have a significant reduction in actin tail formation within RAW cells, which is required for bacterial virulence and spread between host cells. Autophagy inducing compounds have been investigated as potential alternatives to antibiotics, with one compound displaying a level of bacterial killing and autophagy induction in vitro. An AAC has been developed consisting of an anti-CPS antibody conjugated to an antibiotic via a cathepsin cleavable linker. The mechanism of action relies upon opsonisation of Burkholderia and uptake of the AAC into phagocytes. Within the phagocyte, the linker between the antibody and antibiotic is cleaved by cathepsin, therefore releasing the antibiotic in an active form to kill the intracellular bacteria. Two antibiotics have been successfully incorporated into a cathepsin cleavable linker and antibiotic functionality demonstrated in vitro. In conclusion this data is supporting the development of a novel antibody based therapy for melioidosis and gaining insight into the cell-bacterial relationship during Burkholderia infection. This work represents an initial proof of principle in the development of an AAC as a targeted therapy for melioidosis. By targeting intracellular infection it is hoped that this will improve current antibiotic therapy for melioidosis and reduce relapse of infection in infected individuals.