Targeting the superbugs

Impact: Industry collaboration developing new drugs to treat antibiotic resistance

The evolution of antibiotic treatment resistant pathogenic bacteria is arguably the most pressing issue facing health care today.

Without effective antibiotics, a bacterial infection – acquired either in hospital or in the community - may become more commonly life-threatening.  

Medicinal chemists at UOW have been working with industry collaborators over many years to develop more effective antibacterial treatments for pathogenic bacteria of clinical significance including Golden Staph (Staphylococcus aureus), Staphylococcus epidermidis, Enterococcus faecium (VRE), and Clostridium difficle.

The project began in 1998, when UOW initiated a research collaboration with Melbourne-based Avexa Ltd to develop new drugs to fight against vancomycin resistant pathogenic bacteria.

Vancomycin is considered the gold standard for a number of pathogenic bacterial infections, but is being used less and less against susceptible strains for fear of generating additional strains of resistant bacteria. It is therefore kept as a drug of last resort.

Based on the peptide-like structure of vancomycin, the UOW / Avexa team designed and chemically synthesised simpler, but related peptide molecules, which could theoretically bind more strongly to the developing cell-wall of vancomycin resistance bacteria.

This work led to the discovery of a novel series of active peptide-based compounds which showed antibacterial activity generally close to, or better than, that of vancomycin against Golden Staph and Staphylococcus epidermidis, and superior against VRE. Two of these new compounds were licensed by Avexa to European pharmaceutical company, Valevia, for development into Phase 1 clinical trials for topical applications.

With support from the National Health and Medical Research Council, the team is currently developing new compounds to treat gastrointestinal infection caused by Clostridium difficile, an increasing problematic, hospital acquired infection which causes symptoms such as diarrhoea and abdominal pain, and outcomes such as pseudomembranous colitis and toxic megacolon.