Trichothecene toxicity in eukaryotes: Cellular and molecular mechanisms in plants and animals

Trichothecenes are sesquiterpenoid mycotoxins commonly found as contaminants in cereal grains and are a major health and food safety concern due to their toxicity to humans and farm animals. Trichothecenes are predominantly produced by the phytopathogenic Fusarium fungus, and in plants they act as a virulence factor aiding the spread of the fungus during disease development. Known for their inhibitory effect on eukaryotic protein synthesis, trichothecenes also induce oxidative stress, DNA damage and cell cycle arrest and affect cell membrane integrity and function in eukaryotic cells. In animals, trichothecenes can be either immunostimulatory or immunosuppressive and induce apoptosis via mitochondria-mediated or -independent pathway. In plants, trichothecenes induce programmed cell death via production of reactive oxygen species. Recent advances in molecular techniques have led to the elucidation of signal transduction pathways that manifest trichothecene toxicity in eukaryotes. In animals, trichothecenes induce mitogen-activated protein kinase (MAPK) signalling cascades via ribotoxic stress response and/or endoplasmic reticulum stress response. The upstream signalling events that lead to the activation trichothecene-induced ribotoxic stress response are discussed. In plants, trichothecenes exhibit elicitor-like activity leading to the inductions MAPKs and genes involved in oxidative stress, cell death and plant defence response. Trichothecenes might also modulate hormone-mediated defence signalling and abiotic stress signalling in plants.

► Trichothecene mycotoxins inhibit eukaryotic protein synthesis and are toxic to plants, humans and farm animals.
► At the cellular level, they induce oxidative stress, cell-cycle arrest, and apoptosis and affect membrane integrity.
► In animals, trichothecenes manifest toxicity via ribotoxic stress response and endoplasmic reticulum stress response.
► In plants, trichothecenes induce genes involved in oxidative stress, cell death and plant defence signalling.