June 15, 2015  Print

Researchers at the Westmead Millennium Institute for Medical Research have created a ‘wimp’ version of the AIDS-related fungus, Cryptococcus neoformans,the fungal pathogen that causes a million cases of meningo-encephalitis and 600,000 deaths in HIV-infected patients each year.

Researchers at the Westmead Millennium Institute for Medical Research have created a ‘wimp’ version of the AIDS-related fungus, Cryptococcus neoformans, the fungal pathogen that causes a million cases of meningo-encephalitis and 600,000 deaths in HIV-infected patients each year.

The research, published in the journal mBio, identified a metabolic pathway responsible for producing IP7 which is crucial for Cryptococcus to grow and establish life-threatening infections in patients with weakened immune systems, such as those with leukaemia and AIDS, as well as organ transplant recipients.

The discovery could potentially provide a novel avenue for the development of urgently needed anti-fungal drugs.

In collaboration with scientists at University College London, the team at The Westmead Millennium Institute identified the metabolic pathway responsible for producing IP7, a highly phosphorylated form of the sugar inositol, which is essential for normal cellular function.

They then discovered that blocking production of IP7 led to a significantly weaker version of Cryptococcus. This ‘wimp’ or mutant version of the pathogen grows slowly and cannot cause pneumonia or meningitis in mice. Although the mice were infected they did not get sick.

 This ‘wimp’ or mutant version of the pathogen grows slowly and cannot cause pneumonia or meningitis in mice

Dr Julianne Djordjevic, who led the Westmead Millennium research team says, “We believe this discovery could lead to a drug that blocks the enzyme responsible for producing IP7, and therefore block the ability of Cryptococcus to grow in the patient. 

“The drug could be used as stand-alone therapy or in combination with current drugs to treat fungal infections of the blood stream in patients with poorly-functioning immune systems,” she said.

“Because fungal cells are more closely related to human cells than other disease-causing microorganisms such as bacteria and viruses, and fungal pathogens are becoming more drug-resistant, finding new treatments that kill the fungi but are non-toxic to humans is both a challenge and a major health priority,” said Dr Djordjevic.

This is the first study in a medically-relevant fungal pathogen demonstrating the important contribution of IP7 to the establishment of fungal disease.

The Westmead Millennium Institute for Medical Research team working on the project led by Julianne Djordjevic and Sophie Lev include: Cecilia Li, Desmarini Desmarini and Professor Tania Sorrell. 
Collaborators were Adolfo Saiardi (University College London), Anatomical Pathology at Westmead Hospital; and Steve Schibeci and Nicole Fewings from the Centre for Immunology and Allergy Research at The Westmead Millennium Institute for Medical Research.