50 years and counting: searching for the "silver-bullet" or the "silver-shotgun" to mitigate preharvest aflatoxin contamination

Authors: Guo, Baozhu; FOKA, IDRICE CARTHER - Rutgers University; WU, DONGLIANG - University Of Georgia; CLEVENGER, JOSH - Hudsonalpha Institute For Biotechnology; RONG, DI - Rutgers University; FOUNTAIN, JAKE - University Of Georgia

Submitted to: Toxins
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/9/2025
Publication Date: 12/15/2025
Citation: Guo, B., Foka, I.K., Wu, D., Clevenger, J., Rong, D., Fountain, J. 2025. 50 years and counting: searching for the "silver-bullet" or the "silver-shotgun" to mitigate preharvest aflatoxin contamination. Toxins. 17, 596. https://doi.org/10.3390/toxins17120596.
DOI: https://doi.org/10.3390/toxins17120596

Interpretive Summary: Aspergillus flavus is a ubiquitous saprophytic and opportunistic fungal pathogen infecting, colonizing and producing aflatoxin in agricultural commodities worldwide. Since the 1970’s paradigm shifts from management strategies from post-harvest prevention to preharvest genetic evaluation and breeding of resistant crops to fungal infection, over the last 50 years of intense research has revealed much about the understanding of genetic resistance and the factors that affect the complex process of host and A. flavus interaction. For years, the research community has been in search of the proverbial “Silver Bullet”, a single intervention that would have the power to effectively solve the aflatoxin problem. If experience has taught anything, however, it certainly is that the “Silver Bullet” must be replaced with the “Silver Shotgun.” One single solution in isolation is highly unlikely to solve this complex and nuanced issue, but the right combination of efforts pooling our knowledge of host resistance and fungal biology put to work with the right tools (i.e. CRISPR, speed breeding, biotechnology, nanotechnology, and improved forecasting and detection methods) may allow for real and impactful progress to be made in the coming years toward a more secure, sustainable, resilient, and aflatoxin-free food future. This report highlights the “living embryo” theory and “Key Largo” hypothesis that brings the long-established “dogma” of drought stress and possible cause of the exacerbated aflatoxin contamination to the forefront. CRISPR and enhanced plant immunity could provide resistance to a wide range of stresses, both abiotic and biotic.

Technical Abstract: In 2025, it marks two significant milestones for aflatoxin research: 65 years since aflatoxin was first identified in 1960, and 50 years of focused research on preharvest aflatoxin contamination since it was first recognized in 1975. Studies in 1970s revealed that A. flavus could infect crops like maize and produce aflatoxin in the field before harvest and made it possible to investigate the potential genetic resistance in crops to mitigate the issues. Tremendous efforts have been made to learn about the process and regulation of aflatoxin production along with interactions between A. flavus and host plants as influenced by environmental factors. This has allowed for the breeding of more resistant crops, and investigations into the underlying genetic and genomic components of resistance mechanisms in crops like maize and peanut. However, despite decades of studies many questions remain. One established “dogma” is that drought stress, especially when combined with high temperatures, is the single greatest contributing factor to preharvest aflatoxin contamination and is a perennial risk faced throughout the major agricultural production regions of the world. Although there are many reviews summarizing the decades’ long wealth of information about A. flavus, aflatoxin biosynthesis, management and host plant resistance, there are few reports that put the spotlight on why aflatoxin contamination is exacerbated by drought stress which places plants under severe physiological stress and weaken immune systems. Therefore, here we will focus on three major areas of research in maize: the “living embryo” theory and host resistance mechanisms, the “Key Largo hypothesis” and the causes of drought-exacerbated aflatoxin contamination, and recent advancements in CRISPR-based genome editing for enhancing drought tolerance and increasing plant immune responses. This will highlight key breakthroughs and future prospectives for the continuing development of superior crop germplasm and cultivars and for mitigating aflatoxin contamination in food and feed supply chains.