Exploring cutting-edge research into potential new fungicide targets to combat fungal threats to global food security and human health
Beneath the surface of our everyday world rages a silent, invisible war—a conflict spanning hundreds of millions of years between plants and their persistent fungal adversaries. Today, this ancient battle directly impacts global food security and human health, with fungal pathogens destroying up to 23% of global crops pre-harvest and causing nearly four million human deaths annually 6 4 .
Fungal pathogens destroy enough food to feed 600 million people annually, making them one of the greatest threats to global food security.
As resistance to our current antifungal treatments grows increasingly common, scientists are racing against evolutionary time to discover new vulnerabilities in fungal physiology that could lead to next-generation fungicides. This article explores the cutting-edge research revealing potential new targets for fungicidal compounds and how these discoveries might help secure our agricultural and medical future.
Fungal pathogens devastate essential calorie crops (rice, wheat, maize, and soybean) and commodity crops (bananas, coffee, and barley) that form the economic backbone of many developing nations 6 .
The recent spread of Fusarium odoratissimum (Tropical Race 4) to banana plantations in South America exemplifies how quickly these pathogens can jeopardize both livelihoods and global food supplies 6 .
The World Health Organization (WHO) recently issued its first-ever reports on tests and treatments for fungal infections, highlighting their increasing threat—particularly to immunocompromised individuals 7 .
Cryptococcus neoformans alone kills approximately 150,000 people annually, serving as a frequent AIDS-defining illness with current treatments often proving inadequate 4 .
Our primary defense against fungal diseases has been single-target site fungicides—chemicals that inhibit specific enzymes essential to fungal survival. The three main classes (azoles, strobilurins, and succinate dehydrogenase inhibitors) account for approximately 77% of the fungicide market 6 .
While effective, these compounds share a critical vulnerability: fungi can develop resistance through simple point mutations in the target enzymes. This resistance often emerges within just a few years of deployment, rendering once-powerful treatments ineffective 6 .
"The race has become skewed—it is no longer between the plant and the pathogen but between the pathogen and man" 6 .
Current fungicides target essential cellular processes in fungi, with the most successful compounds focusing on:
Inhibited by azoles
Inhibited by benzimidazoles
Inhibited by strobilurins and SDHIs
These targets share three important characteristics: they are essential for fungal survival, distinct from human biology, and vulnerable to chemical inhibition. The challenge is finding new targets that share these characteristics while being less prone to resistance development.
According to fungal pathologists, ideal next-generation fungicides should 6 :
In 2025, scientists at the Stowers Institute for Medical Research and the University of Georgia published a landmark study in PLoS Biology that dramatically advanced our understanding of fungal vulnerabilities 4 . The research team focused on Cryptococcus neoformans, a deadly human pathogen, with the goal of identifying genes absolutely essential for its survival.
The researchers employed a sophisticated genetic technique called transposon mutagenesis sequencing (TN-seq), which they adapted for use in C. neoformans—the first such application in this pathogen 4 .
Bombarding millions of fungal cells with small DNA segments called transposons that randomly insert themselves throughout the genome, disrupting whatever gene they land in.
Allowing the mutated fungal cells to grow and multiply under controlled conditions.
Using DNA sequencing to identify which genes sustained transposon damage in the surviving population.
Applying statistical models to determine which genes could not tolerate disruption—indicating they were essential for survival.
"Fighter planes returning to hangars were mapped for bullet damage to devise ways to strengthen them. However, areas of planes lacking damage were not necessarily better reinforced, but rather were never mapped because they never returned—a phenomenon called survivorship bias" 4 .
The research team identified 1,400 genes essential for C. neoformans survival, including 302 that shared no similarity with human genes 4 . This latter group represents particularly promising targets for new fungicidal compounds, as drugs developed against them would be less likely to cause side effects in humans.
| Gene Category | Number | Significance |
|---|---|---|
| Total essential genes | ~1,400 | Define core biology required for fungal survival |
| Fungal-specific essential genes | ~300 | High potential for selective toxicity |
| Conserved across fungal pathogens | ~30 | Potential for broad-spectrum antifungals |
| Human homologs present | ~1,100 | Higher risk of side effects if targeted |
The study reinforced the value of targeting fungal-specific respiratory proteins in mitochondria 4 6 . Because fungal mitochondria contain unique components not found in human cells, they represent excellent targets for selective inhibition.
This approach builds on earlier work investigating mono-alky lipophilic cations (MALCs), which naturally accumulate in mitochondrial membranes where they can disrupt energy production 6 .
Targeting multiple essential processes simultaneously may be the key to overcoming resistance, as compounds that affect multiple essential genes or pathways would be much more difficult for fungi to evade through simple mutations.
Another promising approach involves double-stranded RNA-based crop protection, which aims to silence selected genes in pathogens to reduce their virulence 2 . This technology brings the promise of exquisite specificity—potentially targeting specific fungal genes while leaving beneficial organisms unaffected.
The biological fungicide market is projected to grow at a robust 7.9% CAGR, reaching $4.1 billion by 2033 5 . These products include:
The biological fungicide market is projected to grow at a 7.9% CAGR, reaching $4.1 billion by 2033 5 .
Despite these promising developments, significant challenges remain:
The fight against fungal pathogens represents an ongoing evolutionary arms race—one that humans cannot afford to lose. The identification of essential fungal genes through innovative techniques like TN-seq represents a paradigm shift in how we approach fungicide discovery.
Rather than relying on incremental improvements to existing chemistries, we can now adopt a target-based approach—identifying vulnerabilities first and then designing compounds to exploit them.
This effort requires unprecedented collaboration between academic researchers (who excel at basic discovery biology) and industry partners (who possess medicinal chemistry and development expertise) 6 .
As climate change and global trade alter disease dynamics, and as immunocompromised populations grow, the need for effective antifungal strategies will only intensify. The genetic insights now emerging from laboratories worldwide offer hope that we can develop a new generation of smart fungicides that protect both our crops and our health without harming the environment—a true victory in the invisible war beneath our feet.