Starving Fungi Could Save Lives2 weeks, 5 days ago
Posted on Jun 27, 2018, 10 p.m.
Millions of lives could be saved each year with a potential new approach that has been identified to treat lethal fungal infections that claims over 1.6 million lives annually by starving the fungi of key nutrients to prevent their growth and spread.
Stopping fungi from producing transporters to distribute nutrients has been found by Westmead Institute researchers to have starved fungi. Despite the human body having high levels of phosphate this study shows infecting fungi are poor at absorbing it, causing the fungi to produce transporters to bring in phosphate. Blocking the phosphate starvation response to inhibit production of transporters prevented their spread in infected mice.
Fungal infections death rates currently are similar to tuberculosis and greater than malaria. Antifungal drugs are poorly absorbed by the body, toxic, and prone to drug resistance making them not fully effective. New therapies are needed to reduce the high mortality rates as no new classes of drugs have been introduced since 1986.
Stopping fungi from absorbing nutrients could provide a treatment path for fungal infections, which is of great importance for patients with compromised immune systems such as seen in patients with leukaemia, HIV/AIDS, or organ transplant recipients. Phosphate starvation response in fungal pathogens expands its function to transport other nutrients, starvation response also occurs as phosphate transporters don’t function properly at human pH; combined lack of nutrient absorption at human pH with expanded starvation response means this blocking could be key to treating potentially lethal infections.
Drugs such as Foscarnet and other FDA approved drugs used to treat viral infections in transplant patients have been shown to inhibit starvation response, used in combination with antifungal drugs prescribed in clinic they work more effectively reducing treatment dose and potential side effects.
Materials provided by Westmead Institute for Medical Research.
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Sophie Lev, Julianne Teresa Djordjevic. Why is a functional PHO pathway required by fungal pathogens to disseminate within a phosphate-rich host: A paradox explained by alkaline pH-simulated nutrient deprivation and expanded PHO pathway function. PLOS Pathogens, 2018; 14 (6): e1007021 DOI: 10.1371/journal.ppat.1007021