The eyes of the world have been focussed on fighting a novel virus. The international public health danger of COVID-19 has been shouting the loudest for the funding, public concern and political attention. But, all the while, a medical timebomb is ticking: the very real danger that antibiotics will stop working.

Since their discovery, antibiotics have saved millions upon millions of lives. Antibiotics together with antifungal drugs are collectively called antimicrobials and they are used in medicine to prevent infection after major surgery and to stop newborns from contracting infections at birth. Antimicrobial drugs treat sepsis and abscesses, diabetic ulcers and tonsillitis. This precious treatment could continue to save countless lives, if it were not for the creeping ability of bacteria and fungi to develop resistance to our drugs.

Over the past thirty years people have not only used antibiotics as a ‘just in case’ medical placebo, but have also used them as cleaning agents in industry, as prophylactic treatments to boost animal growth and for protecting crops. These pre-emptive uses mean that low level doses of antimicrobials are released into our bodies, our soil and water allowing the microbes time and space to develop resistance to established antimicrobial agents. When that happens, infections become very difficult and sometimes even impossible to treat. Resistant strains of the microbes that cause deadly infections are on the rise. The World Health Organisation (WHO) predicts that the number of deaths from antimicrobial resistant (AMR) infections will exceed 10 million a year by 2050.

Universities driving interdisciplinary discovery

The race is now on to find new antimicrobial drugs to take the place of those that have become obsolete. The drive for discovery is very much in the hands of universities around the world as there is a little economic incentive for commercial laboratories to research and develop commodity pharmaceuticals.

Finding new antimicrobial drugs is not simple and necessitates an interdisciplinary approach, with scientists and laboratories with different areas of expertise working jointly to tackle the problem from different angles. In addition, institutions need to work in a complementary way to take initial discoveries by one institution into clinical situations with another.

One such collaboration is happening within the Monash Warwick Alliance, a pioneering higher education partnership between the University of Warwick in the English Midlands and Monash University in Melbourne, Australia.

Professor Greg Challis, holds a joint appointment in the Department of Chemistry and Warwick Integrative Synthetic Biology Centre at the University of Warwick and the Department of Biochemistry and Molecular Biology and ARC Centre of Excellence for Innovations in Peptide and Protein Science at Monash University, and is an expert in chemical and synthetic biology. Professor Challis and his team are working to discover and develop new antibiotics from natural sources to tackle drug resistant bacteria. Professor Ana Traven is Head of the Infection Research Program in the Biomedicine Discovery Institute at Monash University, ARC Future Fellow and an expert in fungal infections and anti-fungal drugs. Professor Traven and her team are working to develop both new antimicrobial drugs to treat fungal infections, and new ways to prime the human immune system against infections so that we do not have to rely so heavily on antifungal drugs.

Together, Traven and Challis co-lead the Monash Warwick Alliance Interdisciplinary Training Programme in Emerging Superbug Threats.

The programme aims to produce a future-ready workforce to tackle antimicrobial resistance and develop promising approaches for the treatment of the most worrying bacterial and fungal infections that plague patients in hospitals. The strategy is to bring together key senior researchers in Chemistry, Biomedical Engineering and Biomedical Sciences to recruit, train and deploy some of the brightest early career researchers from Australia and the UK to the quest for new antimicrobial drugs and other treatments to defray the human cost of drug-resistant infections.

“This program combines Warwick’s expertise in the discovery and development of new antibiotics using cutting edge chemical, structural and synthetic biology techniques with expertise at Monash in a wide range of drug-resistant pathogens and relevant pre-clinical models of infection,” explains Professor Challis.

Professor Traven adds: “Across the alliance we have high-end expertise in all five “urgent threat” microbial pathogens identified by the CDC in their 2019 Antimicrobial Resistance Report. This is rare if not unique internationally and includes not only bacteria but also the less well-known but highly deadly fungi. “

Already pushing the research agenda

You don’t have to look very far to find examples of how the partnership works and is pushing forward the research agenda.

“At Warwick, we are developing antibiotics with activity against several important human pathogens, including Acinetobacter baumannii and Enterobacter cloacae,” continues Professor Challis. “These two drug-resistant bacteria have been identified by the World Health Organisation as a critical priority for the development of new antibiotics. We are also identifying and developing products with action against methicillin-resistant Staphylococcus aureus, Mycobacterium tuberculosis, and Candida albicans. Colleagues at Monash are working to establish the mechanism of action of several of these and test their efficacy in animal infection models. These are key steps along the path to creation of effective new antibiotics that are able to tackle drug-resistant super-bugs.”

“A strength of the Monash – Warwick AMR program is our cross-disciplinarity, particularly in the highly relevant disciplines of microbiology and chemistry that need to be married if we are to find effective antibiotics and antifungals to tackle superbugs,” says Professor Traven.

“The COVID-19 pandemic has shone a light on the importance of investment into infectious diseases research. We designed the Alliance AMR programme to leverage our combined expertise and the highly collaborative nature of our interactions to not only develop new promising drug leads but also, very importantly, boost capacity for infectious diseases research by training the next generation. Our programme has also contributed to the establishment of the Centre to Impact AMR at Monash, whose mission is to unite leaders in Social Sciences, Education, Engineering, Mathematics, Evolution and Microbiology to promote the broadest possible set of sustainable solutions to the problems of AMR. Mitigating the global effects of AMR provides the best future scenario to maximise the impact of new drugs borne from the drug discovery work of the Monash-Warwick Alliance."

The continuing battle against antibiotic resistance needs a workforce that can drive the next wave of discoveries and their translation into the clinic. And this is the Alliance’s vision – to create a world leading international and interdisciplinary training program with industrial and clinical linkages in AMR for early career researchers. The collaboration proposes to build on and enhance the existing strengths in facilities, expertise and complementarity across Monash and Warwick in the wide range of disciplines and technologies needed to tackle AMR, and to make new scientific discoveries that can help tackle this global crisis.

Published:

20 January 2022

About:

Greg Challis is the Monash Warwick Alliance Professor of Sustainable Chemistry. He is working on the discovery, biosynthesis, bioengineering, and mechanism of action of antibiotics and other bioactive metabolites produced by bacteria.

Professor Ana Travens is working to understand how pathogenic fungi cause diseases with the view of building the knowledge foundation for future approaches to anti-infective treatments. She is based at Monash Biomedicine Discovery Institute,

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