A fresh approach to thwart fungal infections by hindering their capacity to produce fatty acids has been found by scientists, which could potentially influence a wide variety of fungal species. By screening the RIKEN natural product depository (NPDepo) and pinpointing a distinct compound, NPD6433, that impedes fatty acid synthase, researchers have shown a significant reduction in fatalities in infected lab worms by nearly 50%. This approach could serve as a valuable alternative to existing treatments which are losing efficacy due to rising drug resistance.
Scientists from the RIKEN Center for Sustainable Research Science (CSRS) and the University of Toronto have shed light on a unique method to combat fungal infections, by targeting the fungus’s capability to generate fatty acids, a crucial constituent of fats.
As resistance to conventional antifungal medications keeps escalating, this ground-breaking approach becomes increasingly significant, particularly considering its innovative mechanism and its extensive impact on diverse fungal species. The scientific journal Cell Chemical Biology published the results of this research.
While most people are aware of conditions like athlete’s foot, a relatively innocuous ailment that can be addressed by visiting a pharmacy, other fungal infections pose a far more serious threat. Fungi like Candida, Cryptococcus, and Aspergillus are accountable for millions of annual deaths. Similar to bacterial resistance to antibiotics, resistance of fungi to medications is on the rise globally, and unless proactive measures are taken, the death toll is set to escalate.
At present, the three major classes of antifungal medications operate by destroying the barrier encapsulating the fungal cells. Interestingly, although they all target the barrier, current treatments are highly specific, indicating that a treatment effective against one fungus species might not work on another.
The research team endeavored to identify an alternate strategy to combat lethal fungi, one that would be effective against a multitude of species. Their strategy started by screening the RIKEN NPDepo against four pathogenic yeasts, identified as critical human pathogens by the World Health Organization. The aim was to find a compound that would impact all four species, indicating potential effectiveness against a wide range of fungi.
The screening led to the identification of multiple compounds that reduced fungal growth by at least 50% across the four species. After dismissing known compounds, researchers were left with three new options. Of these, the compound least harmful to human cells also impeded the growth of Aspergillus fumigatus, a deadly fungal mold for individuals with compromised immune systems. This compound, designated as NPD6433 in the RIKEN NPDepo, was then further investigated.
The researchers examined nearly 1000 different genes to understand how much NPD6433 hindered growth in yeast lacking a copy of a particular gene. It was observed that a decrease in only one gene, fatty acid synthase, made yeast more vulnerable to NPD6433. This implied that NPD6433 probably functions by inhibiting fatty acid synthase, thereby preventing the synthesis of fatty acids inside fungal cells. Further tests revealed that NPD6433, in conjunction with cerulenin (another fatty acid synthase inhibitor), could exterminate numerous yeast species in the culture.
The final test examined the effectiveness of NPD6433 in a live lab model organism, the worm Caenorhabditis elegans, which had been infected with a pathogenic yeast causing systemic infection in humans. The trials demonstrated that treating infected worms with NPD6433 resulted in about a 50% decrease in fatalities. Notably, this was also the case in worms infected with yeast resistant to a standard antifungal medication.
Yoko Yashiroda, the study’s lead author from RIKEN CSRS, asserted that drug-resistant fungi pose an escalating problem, and the development of new drugs provides hope against these evolving threats. Their research proposes that targeting fatty acid synthesis is a promising alternative therapeutic strategy against fungal infections and one that might not necessitate tailor-made solutions for individual species.
Reference: “Identification of triazenyl indoles as inhibitors of fungal fatty acid biosynthesis with broad-spectrum activity” by Kali R. Iyer, et al., 26 June 2023, Cell Chemical Biology.
DOI: 10.1016/j.chembiol.2023.06.005
Table of Contents
Frequently Asked Questions (FAQs) about Fungal Resistance
What new method have researchers discovered to combat fungal infections?
Scientists have found a novel way to fight fungal infections by hindering their ability to produce fatty acids. This approach could potentially impact a wide variety of fungal species.
What is the specific compound that researchers found to inhibit fatty acid synthase in fungi?
The researchers identified a compound, NPD6433, from the RIKEN natural product depository (NPDepo), which inhibits the fatty acid synthase in fungi, thereby blocking their fatty acid production.
How effective was this new approach in reducing fatalities?
In experiments with infected laboratory worms, this approach was found to reduce fatalities by about 50%.
Why is this new method important?
This new method is important because resistance to traditional antifungal drugs is growing. The new approach offers an innovative strategy that could potentially affect a wide range of fungal species.
How is this different from current antifungal treatments?
The current antifungal treatments work by destroying the barrier that surrounds fungal cells and are very specific, meaning that what kills one species of fungus might not kill another. The new method inhibits fatty acid synthase, impacting the internal working of the fungal cells and potentially being effective against a wide range of species.
What are the potential applications of the compound NPD6433?
NPD6433 has been shown to inhibit fatty acid synthase in fungi, thus reducing their growth and survival. It has potential applications in developing new treatments for fungal infections, particularly those caused by drug-resistant species.
Who led this research?
The research was led by Yoko Yashiroda from the RIKEN Center for Sustainable Research Science (CSRS).
More about Fungal Resistance
- RIKEN Center for Sustainable Research Science (CSRS)
- University of Toronto
- Study published in Cell Chemical Biology
- World Health Organization
- Overview on Fungal Infections
- Information on Drug Resistance
7 comments
wait, so you’re telling me this could work on all types of fungi? That’s insane!! science never ceases to amaze me…
Who’d have thought fatty acids had a role in this! You learn somthing new every day, huh?
Intriguing stuff! Got me thinking about the possibilities in treating those nasty, drug-resistant fungi. Can’t wait for further developments!
Wow, this sounds like a game changer! those drug-resistant fungi won’t know what hit ’em. Brilliant work by the researchers!!
Quite an interesting approach! Inhibition of fatty acids could pave the way for some groundbreaking treatments. Exciting times for mycology, eh?
finally, some hope against fungal resistance. Could this be the breakthrough we needed? fingers crossed, more research is defo needed.
Kudos to the RIKEN CSRS and University of Toronto teams! Science like this gives me hope we can stay ahead of these evolving pathogens. keep up the good work!