A team of leading infectious disease scientists from academia and industry have been awarded £17.9 million to identify new drugs to treat fungal infections.
The Wellcome funded project will see researchers based at the University of Dundee, collaborate with the Global Health team, at the global biopharma company GSK, and the Centre for Medical Mycology, at University of Exeter.
This five-year project seeks to identify new antifungal treatments, with an initial focus on Cryptococcus neoformans, a deadly fungus causing meningitis, and Candida auris, which is thought to be the first human pathogenic fungus to have emerged as a result of climate change.
With a very limited drug development pipeline, increasing resistance and poor diagnostics for many fungal pathogens, there is an urgent need to find new, widely-applicable, ways of eliminating fungi.
The initial goal of this project is to generate two new pre-clinical drug candidates for cryptococcal meningitis, ideally with broad-spectrum antifungal potential within low- and middle-income settings.
Cryptococcal meningitis is a very serious and frequently deadly disease which mainly affects people with compromised immune systems.
It is one of the main causes of death for people who are living with HIV, leading to approximately 180,000 deaths every year, according to the World Health Organisation.
Dr Manu De Rycker, Head of Pathogen Biology at Drug Discovery Unit (DDU), University of Dundee said, "While Cryptococcus fungi are found everywhere in the environment, for most people their immune system effectively controls the fungus.
"In immunocompromised patients, the fungus is able to travel in the bloodstream to the brain, where it causes meningitis and high mortality rates.
"Treatments are available but they're long, complicated, not fit for purpose in sub-Saharan Africa, where most of the cases are, and accessibility can be an issue."
In addition, the project will seek to identify drug compounds with broad-spectrum activity, in particular against the often drug-resistant fungus Candida auris, which was first discovered in 2009 in Japan.
Candida auris has since rapidly spread around the globe, including outbreaks in hospitals in South Africa, India, parts of North and South America, Spain and the UK.
It was first detected in the UK in 2013, however numbers remain small, with a total of 637 cases recorded in the UK between its first detection and 2024.
Candida auris causes infection in hospitalised patients or people in long-term care facilities, especially those with devices like intravenous catheters or who are on ventilators and people with compromised immune systems. At its most serious, these infections can lead to death.
Dr De Rycker said, "Candida auris is highly resistant to most available drug treatments and disinfectants.
"Most fungi can't live well at 37 degrees [body temperature] but Candida auris is thought to have gained the ability to survive in hotter conditions as temperatures have risen through climate change, meaning the jump in temperature from outside to inside the body isn't as large.
"It is extremely good at surviving on surfaces, including skin and medical devices, and infections usually happen in hospitals when medical devices are inserted into the body."
Professor Elaine Bignell, Director of Research at the MRC Centre for Medical Mycology, at University of Exeter, said, "Candida auris is a newly emerging, often multi-drug-resistant fungal pathogen that has rapidly risen to global prominence.
"Fatality rates associated with systemic Candida auris infection are reported to exceed 40%, and the incidence of disease is continuing to rise.
"As this fungal species is a persistent coloniser of human skin and clinical devices, hospital outbreaks are common and, once established can be very difficult to control."
Through the partnership, The University of Dundee and GSK will work together on the drug discovery aspect of the project, while the University of Exeter will provide fungal biology and clinical expertise.
Professor Ian Gilbert, Head of DDU, said, "This exciting project brings together world experts in their respective fields, all working together towards solving a major challenge.
"There is a substantial gap we are trying to fill here and a huge need - we're committed to doing this right."
David Barros-Aguirre, Head of Global Health Medicines R&D, GSK, said, "This collaborative research project addresses a critical unmet need highlighted by the World Health Organization, having the potential to improve treatments for cryptococcal meningitis and Candida auris infections.
"Through this research, we hope to not only address the pressing need to get ahead of fungal disease in lower-income countries, particularly for people living with HIV who are disproportionately affected by cryptococcal meningitis, but also to help address the burden of antimicrobial resistance to contribute to long-term health security."
Tim Miles, AMR Portfolio Leader, Global Health Medicines R&D, GSK, added, "By identifying preclinical candidates with distinct mechanisms of action, enhancing infrastructure for antifungal drug discovery, and engaging with scientists from leading academic institutions, we aim to deliver potentially transformative solutions for patients.
"By considering low- and middle-income settings in the design of these novel assets, our hope is that this will lead to possible global solutions to combat the prevalence of fungal infections and emerging antifungal resistance."
Sumi Robson, Research Lead in Infectious Disease at Wellcome, said, "Fungal infections cause around 2.5 million deaths worldwide each year, yet we do not have enough treatments available, and the drug development pipeline is severely limited.
"Bringing together leading cross-sector experts in drug discovery and fungal biology this is an exciting project to strengthen that pipeline. Importantly, it will help develop tools and models that will enable and encourage others to be able to enter the field.
