Antimicrobial resistance (AMR) to single or multiple antibiotics has been found in most bacterial pathogens, leading to concerns about the current treatment options. The identification of new antibiotics that are capable of treating a broad range of BW agents is a high priority.
New antibiotics with different modes of action, particularly those targeting components essential for virulence but not growth of the bacteria, would enable treatment with a reduced chance of developing resistance to the therapy.
Project participants have previously identified the macrophage infectivity potentiator (Mip) protein as a novel antivirulence drug target that is present in multiple BW agents. The Mip protein is key to the functional development of several proteins required for causing disease. Furthermore, researchers have demonstrated that the Mip protein from multiple BW agents are all active proteins that can be inhibited by commercially available drugs demonstrating the druggability of compounds specifically designed to target bacterial Mips.
A group of small molecule inhibitors have been manufactured and shown to inhibit the activity of Mip from several different bacterial pathogens. Importantly, these compounds reduce the toxic effects of BW agents in cells derived from humans. This project aims to enhance the potency of the drugs, test their efficacy against a number of BW agents and ultimately test the drugs in infection models against BW agents.