A team of leading infectious disease scientists from academia and industry has been awarded £17.9 million to identify new drugs to treat fungal infections, addressing a critical gap in global health security. The Wellcome-funded project brings together researchers from the University of Dundee, GSK's Global Health team, and the Centre for Medical Mycology at University of Exeter in a five-year collaborative effort.
The initiative focuses on two particularly deadly fungal pathogens: Cryptococcus neoformans, which causes meningitis, and Candida auris, believed to be the first human pathogenic fungus to emerge as a result of climate change. With a severely limited drug development pipeline, increasing resistance, and poor diagnostics for many fungal pathogens, researchers emphasize the urgent need for new, widely-applicable approaches to eliminate fungi.
Targeting Cryptococcal Meningitis
The project's initial goal is to generate two new pre-clinical drug candidates for cryptococcal meningitis, ideally with broad-spectrum antifungal potential suitable for low- and middle-income settings. Cryptococcal meningitis represents a major global health challenge, particularly affecting immunocompromised patients and serving as one of the main causes of death for people living with HIV.
According to the World Health Organization, cryptococcal meningitis leads to approximately 180,000 deaths annually. Dr. Manu De Rycker, Head of Pathogen Biology at the Drug Discovery Unit (DDU) at University of Dundee, explained the pathogen's mechanism: "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."
Current treatments present significant challenges, particularly in resource-limited settings. "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," De Rycker noted.
Addressing the Candida auris Threat
The project will also target Candida auris, a multi-drug-resistant fungal pathogen that has rapidly gained global prominence since its discovery in Japan in 2009. The fungus has since spread worldwide, with outbreaks reported in hospitals across South Africa, India, North and South America, Spain, and the UK. In the UK, 637 cases have been recorded between its first detection in 2013 and 2024.
Professor Elaine Bignell, Director of Research at the MRC Centre for Medical Mycology at University of Exeter, highlighted the pathogen's severity: "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."
The fungus particularly threatens hospitalized patients and those in long-term care facilities, especially individuals with medical devices such as intravenous catheters or ventilators, and those with compromised immune systems. De Rycker explained the pathogen's unique adaptation: "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."
Collaborative Research Structure
The partnership leverages distinct expertise across institutions. The University of Dundee and GSK will collaborate on drug discovery aspects, while the University of Exeter will provide fungal biology and clinical expertise. Professor Ian Gilbert, Head of DDU, emphasized the project's comprehensive approach: "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 at GSK, outlined the project's broader implications: "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."
Global Health Impact
The initiative addresses a significant global health burden. Sumi Robson, Research Lead in Infectious Disease at Wellcome, provided context on the scale of the challenge: "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."
Tim Miles, AMR Portfolio Leader at GSK's Global Health Medicines R&D, emphasized the project's potential for global impact: "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."
The project represents a significant investment in addressing antimicrobial resistance and strengthening the antifungal drug development pipeline. Robson noted the initiative's broader implications: "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."
