Fungal toxins, also known as mycotoxins or fungal secondary metabolites, are biologically active compounds produced by various fungi that can have deleterious effects on humans, animals, and plants. These toxins contribute to fungal pathogenicity and influence host immune responses, playing a significant role in the establishment and progression of fungal infections as well as in food safety concerns.

Types and Sources of Fungal Toxins

Fungal toxins are diverse in chemical structure and biological activity. They include:

• Mycotoxins: Secondary metabolites produced mainly by filamentous fungi such as Aspergillus, Fusarium, and Penicillium species. Common mycotoxins include aflatoxins, fumonisins, trichothecenes, ochratoxins, and zearalenone. These toxins contaminate crops and food products, posing risks of acute poisoning and chronic diseases such as liver cancer and immunosuppression.
• Peptide toxins: Recently identified peptide-based toxins like candidalysin, produced by Candida albicans, contribute to fungal virulence by damaging host tissues and modulating immune responses.
• High molecular weight toxins: Some pathogenic fungi produce larger toxin molecules implicated in infection establishment, although their characterization remains limited.

Mechanisms of Action and Host Interaction

• Cellular toxicity: Many toxins disrupt cellular membranes, inhibit protein synthesis, or induce oxidative stress, leading to apoptosis or necrosis of host cells.
• Immune modulation: Toxins such as gliotoxin from Aspergillus fumigatus impair immune cell functions, including inhibition of macrophage cytokine secretion and neutrophil reactive oxygen species production, thereby facilitating fungal evasion and persistence.
• Barrier disruption: Studies in murine models show that subepithelial macrophages help protect colonic epithelial cells from fungal toxins like gliotoxin and candidalysin by limiting toxin absorption and maintaining barrier integrity.

Clinical and Environmental Impact

• Human health: Exposure to fungal toxins can result in a spectrum of diseases ranging from allergic reactions and immunosuppression to severe systemic infections and cancer. Opportunistic fungal infections often involve toxin-mediated damage that aids in colonization and invasion, especially in immunocompromised individuals.
• Agriculture and food safety: Mycotoxin contamination leads to significant crop losses and threatens food security globally. The stability of mycotoxins in food products complicates their removal and necessitates rigorous detection and control measures.

Fungal toxins are potent bioactive compounds that contribute to fungal pathogenicity and have significant health and economic implications. Their diverse mechanisms of action impact host immunity and tissue integrity, underscoring the importance of continued research into fungal toxin biology and control strategies.