Drug-resistant fungal infections could be treated by starving fungus: Study

Fungal infection resistant to drugs could be treated by limiting fungus` access to its feed, critical for the organism`s survival, research has found. Researchers repurposed drug to deny drug-resistant fungus of iron, an element crucial to its survival. "In the absence of novel drug candidates, drug repurposing aimed at using existing drugs to treat diseases is a promising strategy," said Mira Edgerton, co-lead investigator of the study.

The research was published in the `Antimicrobial Agents and Chemotherapy`.To treat Candida albicans, common yeast that can cause illness in those with weakened immune systems, researchers limited the fungus` access to iron, an element crucial to the organism`s survival.

They did so by using deferasirox, a medication used to treat blood disorders. Tested in mice, the results were promising: investigators decreased iron levels in saliva by four times, which altered the expression of more than 100 genes by the fungus, diminished its ability to infect oral mucosal tissue and caused a two-fold reduction in the organism`s survival rate.

The investigators found that Candida albicans in the mice who received the treatment were less likely to survive attacks by the immune system, subsisting at a 12 per cent survival rate compared to a 25 per cent survival rate in mice who did not receive the treatment.

Currently, only three major classes of clinical antifungal drugs exist. However, fungal drug resistance has steadily increased and no new classes of antifungals have emerged in decades, said Edgerton. Candida albicans, fungi among the group building resistance, is the agent behind a number of infections.

They include oral thrush, a yeast infection in the mouth identified by a white film that coats the tongue and throat, causing painful swallowing; and denture-related stomatitis.

The yeast is also the fourth leading cause of hospital-acquired bloodstream infections, which often have high mortality rates, said Edgerton.

Candida albicans is the most abundant fungus in the oral microbiome and relies heavily on saliva as a source for essential elements. Iron, the second most abundant metal in saliva, is a critical nutrient used by the fungus in several cellular processes, including energy production and DNA repair.

The study is the first report of iron starvation affecting gene expression of Candida albicans in real time during live infection.

Other research has shown that treatment with deferasirox does not result in iron deficiency in adults with normal iron levels, forming the potential for preventative treatment for those who are also vulnerable to mucosal infections, said Sumant Puri, co-lead investigator.