Investigating fungi and what makes them dangerous
- Wits University
A Wellcome award for first-of-its-kind fungal research in Africa may unlock the origins of human infection.
When Dr Serisha Naicker’s findings in her PhD showed an unexpected cluster of clinical Cryptococcus isolates in Limpopo, Mpumalanga, and Gauteng provinces, she couldn’t have known that such data would one day spark an award-winning research endeavour.
Naicker, a postdoctoral fellow in the Wits Mycology Division and a senior medical scientist at the National Institute for Communicable Diseases (NICD), received a five-year, £2.9 million (approximately R71 million) Wellcome grant. The aim: to uncover how fungi in the genus Cryptococcus, some of which cause deadly meningitis in people living with HIV, evolve in their natural environment and emerge to cause disease. It’s the first large-scale study of its kind in Africa.
Cryptococcus is the leading cause of meningitis among adults in Africa and is responsible for around 112,000 deaths globally each year, 63% of which occur in Africa.
The new study, CryptoADAPT, brings together partners from Wits, the University of Pretoria, Stellenbosch University, Centro de Investigação em Saúde de Manhiça (CISM) in Mozambique, the University of Zambia, Imperial College London in the United Kingdom, and Duke University in the United States.
Investigating the environmental roots of infection
“We’ve always focused on clinical isolates,” Naicker explains, referring to fungi cultured from patient samples. “This time, we’re going into the environment to find out where these cryptococcal species live, how they behave, and what might make them more dangerous or pathogenic.”
The ecological side of Cryptococcus remains vastly underexplored, particularly in Africa. While South Africa has long been a leader in studying the clinical impact of fungal infections, research into their environmental origins is still in its infancy.
Under Naicker, the international research team will collect over 5,000 environmental samples across field sites in South Africa, Zambia, and Mozambique. These include tree hollows, soil, animal droppings, bark beetles and other potential reservoirs of these fungi. Once isolated, the fungal samples will be identified and characterised before being sent to partners in the UK and US for advanced genomic sequencing and stress experiments.
While everyone is exposed to and inhales Cryptococcus at some point in their lives, most people will clear the fungus. Cryptococcal disease becomes life-threatening when the fungus infects immunocompromised people, especially those with advanced HIV disease.
Meanwhile, not all Cryptococcus are pathogenic. One of the central questions of the research is: What causes some species to switch from harmless to harmful? Climate change may be part of the answer. “Higher temperatures could be driving the fungi to become more resilient and more pathogenic,” says Naicker. “We want to understand what kinds of stressors—heat, antifungal exposure, or genetic mutations—trigger this switch.”
This is the first time something like this is being conducted on this scale. The team is going into untouched wilderness areas, rural farms and forests, and there’s a real possibility new species will be found.
Building African research capacity
Another significant component of the grant is training. The project will fund a series of workshops to build capacity in medical and environmental mycology in the partner countries. Early-career researchers will be taught how to isolate, identify, and test fungal strains, an essential skill set in a field that remains severely underfunded.
Professor Nelesh Govender, Director of the Wits Mycology Division and Naicker’s mentor, says this work is part of a broader research mission to reduce AIDS mortality in Africa by tackling its most neglected drivers: serious fungal infections.
"At least a fifth of the 630,000 global AIDS-related deaths are caused by cryptococcal meningitis,” Govender says. “But from autopsy studies, we also know that people with AIDS often die with multiple co-infections. These poor outcomes are linked to a lack of affordable diagnostics, limited access to medicines, and importantly, a glaring gap in research and innovation.”
He emphasises that Africa, bearing the highest burden of HIV, TB and associated fungal diseases, must integrate fungal diagnosis and treatment into essential care packages. “These grants do more than fund science. They help develop a pipeline of African scientists. Serisha is one of our brightest early-career researchers, and this award is not only a personal achievement but a building block in strengthening continental and national capacity,” says Govender. “Ultimately, we must aim for research, testing, diagnostics, and innovation to happen right here, in Africa.”
A chance to change the future of fungal disease
In 2022, the World Health Organization listed Cryptococcus among its highest-priority fungal pathogens requiring urgent investment. For Naicker and her team, this grant represents a long-overdue opportunity to advance science from the ground up.
“We’re literally going back to the roots—into the soil, the trees, the droppings—because that’s where the story of human infection begins,” she says.