Research Field: Biochemistry and structural biology
Dr McMahon’s research ambition is to develop new antimicrobial drugs to treat melioidosis, a tropical bacterial disease resulting from infection with a bacterium called Burkholderia pseudomallei. Melioidosis is endemic in northern Australia and South East Asia, with an estimated ~165,000 cases per year worldwide of which a huge proportion – 89,000 – are fatal. There is no vaccine. Treatment requires 3 months of antibiotics, and yet mortality rates are high, ranging from 10–40% depending on region.
The bacterial DiSulfide Bond (dsb) machinery is a family of folding enzymes that catalyse the formation of disulfide bonds in secreted and membrane proteins, many of which contribute to the ability of the bacteria to cause disease (virulence). Disulfide bonds add “structural bracing” to these virulence proteins so they function properly. Working with a team of microbiologists, she has demonstrated that particular dsb proteins are required for B. pseudomallei virulence in a mouse model of disease. Mice infected with wild-type bacteria die, but those infected with bacteria lacking dsb enzymes all survive. She uses protein crystallography and structure-based drug discovery approaches to characterise these novel drug targets and identify inhibitors that may have the potential to become new drugs for melioidosis.