DsbA Foldases from Multidrug Resistant Pathogens as Targets for New Antimicrobials
In 2014 the World Health Organization declared antimicrobial resistance a global health priority. With 10 million deaths per year predicted by 2050 due to drug resistant infections, new therapies to tackle multidrug resistant pathogens need to be developed now. Drugs targeting bacterial virulence are a promising new class of antimicrobials hailed as evolutionary robust therapeutics for common bacterial infections. We have developed novel inhibitors of DsbA, a protein-folding enzyme (foldase) with a central role in pathogen virulence. In this project we will focus on two clinically important pathogens responsible for >200 million human infections globally pa: uropathogenic Escherichia coli (major cause of urinary tract infections and sepsis) and Salmonella enterica (major cause of foodborne diarrhoea). We have already shown that these pathogens possess multiple DsbA foldases that are structurally and functionally diverse.
Here, using a combination of genetic, biophysical and structural methods, we will characterise the precise role of different DsbA foldases in E. coli urinary tract infection and Salmonella intestinal infection in vitro and in vivo. We will also evaluate the effect of our current crop of DsbA inhibitors against each of these diverse DsbA targets, their potential to attenuate pathogen virulence during infection, human cell toxicity and off-target effects. Overall, this project will generate critical new knowledge on new antimicrobial targets from pathogens of global public health significance and offer timely insight into the application of novel DsbA inhibitors as therapies for antibiotic resistant infections.
Australian and International applicants are eligible to apply. Selected candidates will be required to apply to competitive scholarships through the Faculty of Health, QUT and will be assisted with their applications. PhD scholarships are approx. $(AUD) 27 596pa for 3.5 years full time study. PhD applicants must have completed or be expected to complete a first class hons or a Masters degree (>25% research).
Demonstrated research excellence, such as academic awards, presentations and peer-reviewed publications are desirable, but not essential.
International students must meet entry requirements for QUT https://www.qut.edu.au/research/study-with-us/how-to-apply#Step_1_Entry_requirements.
For more information about scholarships and postgraduate study at QUT https://www.qut.edu.au/research/study-with-us.