On all fronts
NHMRC funding to fight infectious disease
Infectious diseases are in the firing line of University of Queensland researchers, thanks to significant new funding from the National Health and Medical Research Council (NHMRC).
UQ’s School of Chemistry and Molecular Biosciences and Institute of Molecular Bioscience researchers are at the forefront of this discovery, landing a significant share of the $25 million NHMRC Ideas Grants funding received by the University.
The newly-funded projects will research the role of genomics in the novel coronavirus, how to tackle antibiotic resistance, test novel therapeutics to fight fungal infection, create tools to probe certain viruses and research the potential links between obesity and viral infections.
Superbug-fighting project with potential
Dr Alysha Elliott from IMB is forging a new weapon in the fight against superbugs – and it’s not antibiotics.
Instead, she is using non-antibiotic drugs to increase the potency of existing antibiotics to which bacteria have become resistant.
“Disease-causing bacteria are increasingly becoming resistant to treatment with a single drug,” Dr Elliott said.
“Clinicians are thus forced to administer combination therapies of antibiotics to save patients’ lives, however, such ‘cocktail’ therapies can induce multi-drug resistance in bacteria.
“In recent years, the concept of using non-antibiotic drugs called ‘potentiators’ to increase the activity of existing antibiotics has attracted considerable interest.
“This approach can resuscitate an antibiotic from becoming obsolete due to resistance, and can also minimise the development of new resistance, and expand the activity of the parent antibiotic."
Dr Elliott is leading a project that has identified compounds with no antimicrobial activity in their own right, but that amplify the activity of several antibiotics against Gram-negative bacteria.
“Our investigation will comprehensively assess the effectiveness of these compounds and their propensity to induce drug resistance,” Dr Elliott said.
“These antibiotic ‘potentiators’ are an exciting approach to extend the lifetime of existing antibiotics and address the urgent crisis of antibiotic resistance.”
Media: IMB Communications, communications@imb.uq.edu.au, +61 (0) 405 661 856.
Dr Alysha Elliott from IMB is forging a new weapon in the fight against superbugs (Image: The University of Queensland).
Dr Alysha Elliott from IMB is forging a new weapon in the fight against superbugs (Image: The University of Queensland).
Dr Loic Yengo (Image: The University of Queensland).
Dr Loic Yengo (Image: The University of Queensland).
Exploring the genomics of SARS-CoV-2
The coronavirus SARS-CoV-2 has infected more than 70 million people worldwide, with more than 1.5 million deaths from COVID-19.
Dr Loic Yengo from the Institute for Molecular Bioscience (IMB) is harnessing the power of genetic analysis to uncover why some people develop a more severe case of the disease than others.
Dr Loic Yengo (Image: The University of Queensland).
“While the majority of people infected with COVID-19 exhibit mild symptoms, such as loss of smell, others develop severe respiratory distress syndromes, some of which can be fatal,” Dr Yengo said.
“We hypothesise that part of these differences between individuals is caused by genetic factors in the human host, as reported before in other diseases.”
The NHMRC funding will allow Dr Loic and collaborators to integrate genetic data from two large European biobanks with more than half-a-million participants with local COVID-19 samples.
“In this project, we seek to discover genetic factors that can contribute to explaining these differences. Our findings have the potential to inform the design and analysis of clinical trials for vaccines and treatments.”
Dr Yengo said the statistical methods developed in this project will be general and could be applied to other infectious diseases.
Media: IMB Communications, communications@imb.uq.edu.au, +61 (0) 405 661 856.
An intelligent approach to get a handle on superbugs
Drug-resistant infections threaten to cause 50 million deaths per year worldwide by 2050, but there is a near-empty pipeline of new antibiotics.
IMB's Associate Professor Mark Blaskovich is leading two projects that will tackle the global health challenge of superbugs.
Associate Professor Mark Blaskovich (Image: The University of Queensland)
“New strategies are urgently needed to treat the rise of infections from multidrug-resistant bacteria, with bacteria becoming resistant to standard antibiotic therapies,” Dr Blaskovich said.
"It is still not clear how to design a better antibiotic, and understanding the desirable chemical properties would help.
“For one project, we will apply artificial intelligence methods to study a unique dataset of compounds crowdsourced from over 300 academic groups from all around the world to develop predictive models for antibacterial activity and membrane penetration.
“We will then apply these models to design new antibiotics, which will be synthesised and tested for antimicrobial activity.”
The crowdsourcing initiative – the Community for Open Antimicrobial Drug Discovery (CO-ADD) – has drawn from researchers in 47 countries to screen over 300,000 unique compounds over the past five years.
The second project led by Dr Blaskovich will take a different approach to design new antibiotics, this time using a strategy of modifying existing antibiotics to add extra activity.
“We will build on a unique research platform where we have modified representatives of all major classes of antibiotics with a ‘handle’ at a site where antibiotic activity is unaffected.
“These handles can then be readily modified to attach different functions, such as combining different antibiotics, or adding moieties that increase the potency of an antibiotic through strategies such as improving its cellular penetration, blocking bacterial virulence, or by activating our immune system to fight off the bacteria.”
Dr Blaskovich and colleagues will test the new antibiotics created through this process and optimise them for preclinical trials, where they will be tested for safety and efficacy.
Media: IMB Communications, communications@imb.uq.edu.au, +61 (0) 405 661 856.
Associate Professor Mark Blaskovich (Image: The University of Queensland)
Associate Professor Mark Blaskovich (Image: The University of Queensland)
Ready to probe the intricacies of the world's flaviviruses, Dr Daniel Watterson (Image: The University of Queensland).
Ready to probe the intricacies of the world's flaviviruses, Dr Daniel Watterson (Image: The University of Queensland).
The dengue virus structure (pictured) is now being analysed at an unprecedented resolution (Image: The University of Queensland).
The dengue virus structure (pictured) is now being analysed at an unprecedented resolution (Image: The University of Queensland).
Ready to probe the intricacies of the world's flaviviruses, Dr Daniel Watterson (Image: The University of Queensland).
Creating atomic blueprints for flavivirus vaccines
Dr Daniel Watterson and his UQ team have recently developed an extremely powerful toolset to probe a unique family of viruses.
Flaviviruses are viruses often-transferred via insects such as ticks and mosquitos, including the West Nile virus, dengue virus, tick-borne encephalitis virus, yellow fever virus and Zika virus.
"Flaviviruses are a global problem in desperate need of solutions," Dr Watterson said.
"An effective vaccine for dengue virus is still not available despite more than 400 million infections each year.
"Meanwhile, the rapid emergence and spread of the neurovirulent Zika virus shows the worrying potential for novel flavivirus pandemics.
The dengue virus structure (pictured) is now being analysed at an unprecedented resolution (Image: The University of Queensland).
"This new funding will allow us to probe flavivirus structure and function at the atomic level.
"We're able to continue our work determining flavivirus structures with unprecedented speed and resolution, and have begun to reveal the inner workings of flavivirus architecture and maturation.
"Working together with Associate Professor Fasséli Coulibaly, from Monash University, the team has already discovered 'pockets' in the flavivirus structure, which are a common structural feature of flaviviruses.
"Discoveries like these will allow us to design safer and more effective flavivirus vaccines and therapies."
Media: Dr Daniel Watterson, d.watterson@uq.edu.au, +61 422 098 299; Dominic Jarvis, dominic.jarvis@uq.edu.au, +61 413 334 924.
Investigating obesity and its ‘legacy effect’ on viral infection
Virologist and NHMRC Ideas Grant recipient, Dr Kirsty Short (Image: The University of Queensland).
Obesity is an important risk factor for severe influenza viral infections, and newly-funded research by Dr Kirsty Short and her team will investigate the potential alarming post-obesity risks following viral infections.
“While COVID-19 has been making recent headlines, another pandemic has been prevalent in developed countries – obesity,” Dr Short said.
“In Australia, more than 60 per cent of adults and 25 per cent of children are overweight or obese.
“And obesity increases both the respiratory and extra-respiratory complications of influenza virus and potentially other viruses, like COVID-19.
“We've now got early indications that obesity - even when treated through weight loss- may leave a ‘legacy effect’ when it comes to viral infection.
(Image: Wikimedia).
“Mice who’ve recovered to a healthy size, but have a history of obesity, have a more severe primary influenza virus infection than mice that have never been obese.
“NHMRC funding will allow us to investigate this further, and this project hopes to identify the lasting effects that this obesity epidemic will have on the susceptibility of the Australian population to severe viral infections.
“Hopefully we'll generate highly significant fundamental knowledge about trained immunity and identify and potentially treat an over-looked, high-risk patient group.
“We want to know why weight loss may be insufficient to reverse obesity-associated virus risks, when weight loss should ideally occur in the life course and how we can reverse this phenomenon.”
Media: Dr Kirsty Short, k.short@uq.edu.au, +61 452 374 811; Dominic Jarvis, dominic.jarvis@uq.edu.au, +61 413 334 924.
Virologist and NHMRC Ideas Grant recipient, Dr Kirsty Short (Image: The University of Queensland).
Virologist and NHMRC Ideas Grant recipient, Dr Kirsty Short (Image: The University of Queensland).
(Image: Wikimedia).
(Image: Wikimedia).
(L-R) Dr Minh-Duy Phan, Dr Nhu Nguyen and Prof. Mark Schembri were awarded ~$1.1M to understand how antibiotic resistant E. coli superbugs cause urinary tract and bloodstream infections' (Image: The University of Queensland).
(L-R) Dr Minh-Duy Phan, Dr Nhu Nguyen and Prof. Mark Schembri were awarded ~$1.1M to understand how antibiotic resistant E. coli superbugs cause urinary tract and bloodstream infections' (Image: The University of Queensland).
Fighting antibiotic resistance
Urinary tract infections (UTIs) are one of the most common bacterial infections and are a major driver of new and emerging antibiotic resistance.
Around 150 million cases are recorded globally per year, caused mainly by E. coli bacteria.
As existing antibiotics increasingly fail to treat the disease, Professor Mark Schembri and his team are on a mission to find new targeted treatments.
“Approximately 50 per cent of women and five per cent of men are predicted to develop a UTI in their lifetime,” Professor Schembri said.
“Almost a quarter of women who suffer from a UTI will experience a recurrence within six months of the initial infection.
“Recurrent UTIs are linked with increasing antibiotic resistance, treatment failure, decreased quality of life for the patient and mounting pressure on our healthcare system.
“UTIs are also a major precursor to sepsis, a life-threatening disease with a mortality rate between 20–40 per cent in countries like Australia."
"Among the different types of E. coli that cause UTIs and sepsis, one type known as ST131 is the most common globally.
"E. coli ST131 is highly antibiotic-resistant, causing severe infections with few treatment options, and frighteningly, E. coli ST131 infections are only one step away from being untreatable.
"This NHMRC funding will allow us to dissect and unravel the features of E. coli ST131 that enable it to cause disease, allowing us to explore new targeted treatments to reduce the incidence of UTIs and sepsis."
Professor Mark Schembri, m.schembri@uq.edu.au, +61 433 897 071; Dominic Jarvis, dominic.jarvis@uq.edu.au, +61 413 334 924.
Designing new therapeutics for fungal infections
Approximately 1.5 million people per year succumb to invasive pathogenic fungal infections caused by fungal species Candida spp, Cryptococcus neoformans and Aspergillus fumigatus, making them some of the most deadly communicable diseases.
Amongst hospitalised patients, these infections are becoming more prevalent and more difficult to treat due to drug resistance.
UQ's Professor Luke Guddat and his team are hoping to introduce new weapons to help in the fight against deadly fungal infections.
"Invasive fungal infections are a major threat to human health, especially in patients whose immune system is compromised, like those suffering from HIV, cancer, organ transplant patients, as well as infected patients in underdeveloped countries," Professor Guddat said.
"There is growing concern for the rise of new strains of fungal infections that are resistant to one or more of the current drugs.
"This grant will help us create new therapeutics that block the activity of an enzyme - acetohydroxyacid synthase (AHAS) - whose function is needed for the survival of these pathogens.
"AHAS is not found in humans, so it has a major advantage for drug discovery since inhibitors that target the enzyme are not likely to be toxic to the human host.
"And importantly, this enzyme has not previously been used as a target for antifungal drug therapies, so there will be no pre-existence of resistant strains."
Media: Dr Luke Guddat, luke.guddat@uq.edu.au, +61 447 123 584; Dominic Jarvis, dominic.jarvis@uq.edu.au, +61 413 334 924.
A medical illustration of a drug-resistant fungus, Aspergillus fumigatus (Image: Stephanie Rossow/CDC).
A medical illustration of a drug-resistant fungus, Aspergillus fumigatus (Image: Stephanie Rossow/CDC).
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