Starving fungi could save millions of lives each year

June 22, 2018, Westmead Institute for Medical Research

Researchers have identified a potentially new approach to treating lethal fungal infections that claim more than 1.6 million lives each year: starving the fungi of key nutrients, preventing their growth and spread.

The team from the Westmead Institute for Medical Research found that stopping fungi from producing transporters that carry essential nutrients, like , starved the fungi.

Despite high levels of phosphate in the human body, the research showed that the infecting fungi are very poor at absorbing it. This causes the fungi to produce more transporters to try to bring in more phosphate—a process known as the 'phosphate starvation response'.

By blocking this phosphate starvation response—and stopping the fungi from producing more transporters to get more nutrients—the research team starved the fungi, preventing their spread of in mice.

Lead researcher, Associate Professor Julianne Djordjevic, is optimistic this discovery will provide a new avenue to develop safer and urgently needed antifungal drugs.

"Death rates due to are similar to those of tuberculosis and greater than those due to malaria," Associate Professor Djordjevic said.

"Current antifungal drugs are toxic, poorly absorbed by the body, and not fully effective. Drug-resistance is also emerging as a serious problem.

"Although new therapies are desperately needed to reduce the high global morbidity and mortality of infectious fungal diseases, no new classes of have been introduced into clinical medicine since 1986.

"If we can stop fungi from absorbing nutrients during infection, this could provide a novel treatment avenue for fungal infections. This is particularly important in patients with weakened immune systems, such as those with HIV/AIDS or leukaemia, and in organ transplant recipients who require life-long immunosuppressive therapy," she said.

The first author on the study, Dr. Sophie Lev, expanded the findings using bioinformatics.

"We found that the phosphate starvation response in fungal pathogens has expanded its function to transport other essential nutrients, like sugars and amino acids, not just phosphate. We also identified that this starvation response occurs because phosphate transporters do not function properly at human pH.

"The combined effect of poor nutrient absorption at human body pH and the expanded nutrient starvation response means that blocking this response could be the key to starving fungi of a range of key nutrients and treating these potentially lethal infections," Dr. Lev said.

"This finding is particularly exciting, because we may not need to start from scratch to identify drugs that block the fungal nutrient starvation response.

"FDA-approved drugs like Foscarnet, which are used to treat viral infections in transplant patients, have been shown to inhibit the phosphate in .

"When used in combination with prescribed in the clinic, these drugs work more effectively, reducing treatment dose and potentially side effects," Dr. Lev concluded.

Explore further: A step towards a new drug to treat fungal infections that kill 1.6 million people annually

More information: Sophie Lev et al, 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). DOI: 10.1371/journal.ppat.1007021

Related Stories

A step towards a new drug to treat fungal infections that kill 1.6 million people annually

October 10, 2017
A team from Sydney's Westmead Institute for Medical Research is a step closer to developing a drug to treat life-threatening fungal infections that cause more than 1.6 million deaths annually.

Resistance to antifungal drugs could lead to disease and global food shortages

May 17, 2018
Growing levels of resistance to antifungal treatments could lead to increased disease outbreaks and affect food security around the world.

New study targets lethal fungal infection

July 24, 2017
The development of new drugs to fight a common fungal pathogen which kills half a million people globally each year is a step closer thanks to a University of Queensland-led study.

Researchers explore little-known, deadly fungal infections

April 10, 2018
A new study by Althea Campuzano, Ph.D. a student at The University of Texas at San Antonio, and Floyd Wormley, Jr., Professor of Biology and Senior Associate Dean for Research and Graduate Studies, sheds light on little-known ...

Intestinal fungi may aid in relief of inflammatory disease

June 23, 2016
Fungi that live in a healthy gut may be as important for good health as beneficial intestinal bacteria, according to new research conducted at Weill Cornell Medicine.

Recommended for you

Researchers discover influenza virus doesn't replicate equally in all cells

September 19, 2018
The seasonal flu is caused by different subtypes of Influenza A virus and typically leads to the death of half a million people each year. In order to better understand this virus and how it spreads, University of Minnesota ...

Drugs that stop mosquitoes catching malaria could help eradicate the disease

September 18, 2018
Researchers have identified compounds that could prevent malaria parasites from being able to infect mosquitoes, halting the spread of disease.

Vaccine opt-outs dropped slightly when California added more hurdles

September 18, 2018
In response to spiking rates of parents opting their children out of vaccinations that are required to enroll in school—and just before a huge outbreak of measles at Disneyland in 2014—California passed AB-2109. The law ...

New evidence of a preventative therapy for gout

September 17, 2018
Among patients with cardiovascular disease, it's a common complaint: a sudden, piercing pain, stiffness or tenderness in a joint that lasts for days at a time with all signs pointing to a gout attack. Gout and cardiovascular ...

"Atypical" virus discovered to be driver of certain kidney diseases

September 14, 2018
An international research team led by Wolfgang Weninger has discovered a previously unknown virus that acts as a "driver" for certain kidney diseases (interstitial nephropathy). This "atypical" virus, which the scientists ...

Flu shot rates in clinics drop as day progresses, but nudges help give them a boost

September 14, 2018
Primary care clinics experienced a significant decline in influenza vaccinations as the day progressed, researchers from Penn Medicine report in a new study published in JAMA Open Network. However, "nudging" clinical staff ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.