Dr Andrew Munkacsi
Many of us have heard of antibiotic-resistant bacteria, either through the media or perhaps knowing someone who died from such a bacterial infection. Just as there are bacterial infections resistant to antibiotics, there are fungal infections resistant to antifungal drugs.
Fungi are microbial organisms (not visible to the naked eye) that can infect plants, animals and humans. Yes, mushrooms are fungi, but not all fungi are mushrooms. Approximately 300 fungal species are known to be pathogenic to humans; these include well-known species such as Candida albicans (the causal agent of vaginal yeast infection and oral thrush) as well as the numerous species that cause athlete’s foot.
Unfortunately, not all fungal infections are able to be treated successfully. Fungal infections cause approximately 1 million deaths per year, an alarming number that exceeds the annual deaths caused by breast cancer as well as those caused by malaria. And though people are not currently dying from vaginal yeast infections, oral thrush or athlete’s foot, there is potential for these fungal species to evolve resistance to antifungal drugs.
A recent article published in The New York Times (6 April 2019) profiled Candida auris, a fungus (specifically a yeast) resistant to antifungal drugs, spreading around the world killing a significant number of people since 2009. Prolonged exposure to high doses of antifungals (as in people with compromised immune systems such as the ageing senior population, cancer patients receiving radiation or chemotherapy treatment, and organ transplant patients), is a means for C. auris, and other fungi, to evolve resistance.
The current clinically-approved antifungal drugs are divided into four classes based on their mechanisms, or ways they work. This means a fungus has to overcome merely four mechanisms in order to become resistant to currently-available drug treatment. One potential solution to treating C. auris is combination therapy where lower doses of more than one drug will be used to treat an infection. However, this solution is limited as some drugs cannot be combined.
Developing new antifungals
For these reasons, it would be ideal to identify and develop a new antifungal drug that works by a new mechanism distinct from the current four classes of today’s drugs; this would add another hurdle in the path to resistance. Developing a drug that will target the fungus only and not affect the biology of uninfected cells in the body is not easy and is the reason why there is a shortage of antifungal drugs.
Nature is a proven source to discover the next generation of antifungal drugs as most existing antifungal drugs have been based on natural compounds. As C. auris has not yet been reported in New Zealand, our plants and soil may contain the key to an antifungal drug effective at combatting C. auris.
Research in my lab at Victoria University of Wellington, in collaboration with Drs Rob Keyzers and Michael Jackson as well as the feijoa breeder Nigel Ritson at Foretaste Feijoa Fruit Ltd (Takaka), has identified compounds in the peels of feijoa that inhibit the growth of Candida species that are closely related to C. auris; this work was recently published in The Journal of Agricultural and Food Chemistry. These compounds work by targeting fungal-specific molecules that are not targeted by the four classes of today’s antifungal drugs – thus it will be good to test these compounds against C. auris and other antifungal-resistant species.
Dr Andrew Munkacsi is a senior lecturer in chemical genetics at Victoria University of Wellington.