AntiVirulence Compounds (Dec 2017)

Bio-warfare agents cause potentially lethal infections and many species are multi-drug resistant. As a result, there is an urgent requirement for new treatment regimes and antibiotics.

DMTC’s collaboration with research partners at the University of Western Australia, DST Group, the Peter Doherty Institute and the University of Wurzburg is focused on delivering novel anti-virulence compounds, which are active against potential bio-warfare agents including Burkholderia pseudomallei, the known causative agent of the disease melioidosis.

These novel inhibitors directly target the macrophage infectivity potentiator (Mip) protein, conserved in a number of bacterial species, meaning that the treatment effectively tackles the virulence factor while reducing the chance of developing resistance to the therapy.

The project team has investigated the broad-spectrum activity of these novel compounds and to begin with has demonstrated that they successfully inhibit the Mip protein from the Coxiella burnetii pathogen.

As a result of this finding, the project team has also initiated gene-based studies with the Coxiella Mip protein to investigate its role in the ability of this pathogen to cause disease.

Structural studies are also being used as a guide to improve inhibitors to achieve enhanced efficacy. These modified inhibitors have been synthesized and are now ready to screen, first against the Mip protein itself and then in in vitro infection tests against the bio-warfare pathogens.