Starving fungi could save millions of lives each year

June 21, 2018

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 phosphate, 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 infection 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 fungal infections 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 drug 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 starvation response in fungi.

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


Westmead Institute for Medical Research

Related Amino Acids Articles from Brightsurf:

Igniting the synthetic transport of amino acids in living cells
Researchers from ICIQ's Ballester group and IRBBarcelona's Palacín group have published a paper in Chem showing how a synthetic carrier calix[4]pyrrole cavitand can transport amino acids across liposome and cell membranes bringing future therapies a step closer.

Microwaves are useful to combine amino acids with hetero-steroids
Aza-steroids are important class of compounds because of their numerous biological activities.

New study finds two amino acids are the Marie Kondo of molecular liquid phase separation
a team of biologists at the Advanced Science Research Center at The Graduate Center, CUNY (CUNY ASRC) have identified unique roles for the amino acids arginine and lysine in contributing to molecule liquid phase properties and their regulation.

Prediction of protein disorder from amino acid sequence
Structural disorder is vital for proteins' function in diverse biological processes.

A natural amino acid could be a novel treatment for polyglutamine diseases
Researchers from Osaka University, National Center of Neurology and Psychiatry, and Niigata University identified the amino acid arginine as a potential disease-modifying drug for polyglutamine diseases, including familial spinocerebellar ataxia and Huntington disease.

Alzheimer's: Can an amino acid help to restore memories?
Scientists at the Laboratoire des Maladies Neurodégénératives (CNRS/CEA/Université Paris-Saclay) and the Neurocentre Magendie (INSERM/Université de Bordeaux) have just shown that a metabolic pathway plays a determining role in Alzheimer's disease's memory problems.

New study indicates amino acid may be useful in treating ALS
A naturally occurring amino acid is gaining attention as a possible treatment for ALS following a new study published in the Journal of Neuropathology & Experimental Neurology.

Breaking up amino acids with radiation
A new experimental and theoretical study published in EPJ D has shown how the ions formed when electrons collide with one amino acid, glutamine, differ according to the energy of the colliding electrons.

To make amino acids, just add electricity
By finding the right combination of abundantly available starting materials and catalyst, Kyushu University researchers were able to synthesize amino acids with high efficiency through a reaction driven by electricity.

Nanopores can identify the amino acids in proteins, the first step to sequencing
While DNA sequencing is a useful tool for determining what's going on in a cell or a person's body, it only tells part of the story.

Read More: Amino Acids News and Amino Acids Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.