Fungal infections affect around 600 million people globally each year, and result in around 2.5 million deaths annually.
For those who are susceptible to fungal infections, particularly people who are immunocompromised, an infection can be deadly.
When people are diagnosed with HIV, cancer, diabetes or need an organ transplant, the disease and/or treatment to save their life can make them vulnerable to a new range of illnesses including fungal diseases.
Julianne Djordjevic is a Senior Hospital Scientist and has come up with an innovative approach to treating fungal infections which has the potential to slow the development of resistance.
“So much money has gone into improving the technology to increase the success of an organ transplant and cancer treatments,” Julianne said.
“However, the success of these technological advancements is under threat as treatment options for the secondary illnesses, like fungal disease, are either too toxic or becoming inefficient due to the development of resistance,” Julianne said.
With recent PhD graduate Dr Desmarini Desmarini, Julianne developed a series of compounds in collaboration with Monash University, which act as metabolic blockers.
Thier study from Westmead Institute Medical Research (WIMR) Centre for Infectious Diseases and Microbiology was published in the journal ACS Infectious Diseases and the compound series featured in the 2025 WHO preclinical antifungal pipeline report aimed at combating antimicrobial resistance.
Their lead compound, DT-23, an inositol polyphosphate kinase (IPK) inhibitor, prevents the fungus from replicating.
It does this by blocking the fungus’ capacity to sense its own energy reserves. The block in energy sensing occurs at two sites, slowing the development of resistance.
Current therapies, which hit only a single target, are prone to resistance development.
The fungus has the energy to reproduce and multiply but when the compound is administered, it blocks production of the energy sensor, meaning it tricks the fungus into thinking it doesn’t have the energy it needs to multiply or reproduce, so it starves.
“Fungal diseases are difficult to treat without causing sides effects, due to their likeness to human cells, and patients undergoing cancer treatment will already be experiencing a range of side effects from their treatment,” Julianne said.
Due to the differences in the energy sensing pathways of fungi and humans, Julianne is hopeful that another advantage of the DT-23 metabolic blocker will be less side effects for the patient.
Already proving a success in insect trials using wax moth larvae, the next phase of the trial will attempt to replicate the same success in mice.
Desmarini was among the first students to receive a PhD scholarship for a recently initiated, Industry PhD partnership program, to conduct this study.
“Combining DT-23 with a commonly used antifungal that is toxic to the kidneys, more potently kills fungi than either drug alone”, Desmarini said.
“We have shown that this drug synergy extends to protection against a fungal infection in the wax moth model” Desmarini said.
“To be able to provide a drug to treat a fungal infection with minimal side-effects and reduced potential for the fungus to develop resistance would be so impactful to treatment outcome,” Desmarini said.