A preclinical evaluation pipeline for new antivirulence drugs targeting multidrug resistant bacterial pathogens

Overview

A post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century.’ - WHO, 2014 (1). Antimicrobial resistance (AMR) is a global public health priority. If no action is taken, AMR is predicted to kill more people than cancer and diabetes combined by 2050, with 10 million deaths estimated each year and a global cost of up to 100 trillion USD. New therapies to tackle multidrug resistant (MDR) pathogens are sorely needed.

My lab, in collaboration with scientists from Australia and the US has developed novel antimicrobials that aim to disarm (anti-virulence) rather than kill (antibiotics) bacterial pathogens. These novel antimicrobials can offer superior therapeutics, as they can be more evolution-proof and narrow-spectrum than traditional antibiotics (2). These benefits need however to be evaluated in relevant preclinical models before further clinical development.

Aims

• To establish relevant in vitro models of antibiotic resistant infection.
• To evaluate our current virulence inhibitors as therapies in these models.

References / key papers

1. World Health Organization, Antimicrobial Resistance: Global Report on Surveillance (2014).
2. Totsika, M. (2016) Benefits and Challenges of Antivirulence Antimicrobials at the Dawn of the Post-Antibiotic Era, Drug Delivery Letters 6, 8.

Approaches/skills and techniques

Culture of human cell lines, handling/culturing multidrug resistant bacterial pathogens and GMOs, gene expression analysis (DNA/RNA isolation, protein preparation, PCR, qRT-PCR, DNA/protein gel-electrophoresis, etc), in vitro cell infection assays. You will also receive training in conducting literature searches and critical literature review, research design and methodology, data analysis and presentation in lab meetings.
Outcomes

The preclinical pipeline set up will provide a relevant platform for the identification and development of antivirulence drugs as therapeutics for common multidrug resistant infections, such as urinary tract infections and diarrhoea

Required skills and experience

An ideal candidate will have an active interest in microbiology, infectious diseases and/or drug development. Prior study in these areas would be desirable.

Keywords

• antibiotic resistance
• antivirulence
• infections
• biofilm
• novel antimicrobials
• multidrug resistance

Contact

Please contact Associate Professor Makrina Totsika for more information.