Inhibition of the immunophilin family of proteins

Immunophilins are a family of peptidyl-prolyl cis-trans isomerases that are present in bacterial pathogens. The immunophilins are involved in protein folding and are important in maintaining protein stability and function, with many studies showing that immunophilins are needed for the proper function of virulence determinants.

In this project, we are investigating a series of small molecule inhibitors that can prevent immunophilin function in bacteria and interfere with virulence and the capacity to cause disease.

We are focused on the intrinsically antibiotic resistant bacteria, Burkholderia pseudomallei, which is the causative agent of melioidosis and has a fatality rate of up to 15 per cent in Northern Australia.

Our main goal for this project is to screen small molecule inhibitors of immunophilins to test the ability of these inhibitors to reduce bacterial virulence in models of infection.

Our research team lead for this project is Dr Mitali Sarkar-Tyson, a research fellow within UWA’s School of Biomedical Sciences. We are collaborating with Professor Ulrike Holzgrabe from the University of Würzburg and Professor Tim Atkins from the Defence Science Technology Laboratories in the United Kingdom. We have also received significant funding from the Defence Material Transfer Centre in Australia, the Defence Science Technology Laboratories in the UK, and the European Union’s North Atlantic Treaty Organization.