PT - JOURNAL ARTICLE AU - Xing Zhang AU - Benjamin Harding AU - Dina Aggad AU - Damien Courtine AU - Jia-Xuan Chen AU - Nathalie Pujol AU - Jonathan J. Ewbank TI - Antagonistic fungal enterotoxins intersect at multiple levels with host innate immune defences AID - 10.1101/2020.11.23.391201 DP - 2020 Jan 01 TA - bioRxiv PG - 2020.11.23.391201 4099 - http://biorxiv.org/content/early/2020/11/23/2020.11.23.391201.short 4100 - http://biorxiv.org/content/early/2020/11/23/2020.11.23.391201.full AB - Animals and plants need to defend themselves from pathogen attack. Their defences drive innovation in virulence mechanisms, leading to never-ending cycles of co-evolution in both hosts and pathogens. A full understanding of host immunity therefore requires examination of pathogen virulence strategies. Here, we take advantage of the well-studied innate immune system of Caenorhabditis elegans to dissect the action of two virulence factors from its natural fungal pathogen Drechmeria coniospora. We show that these two enterotoxins have strikingly different effects when expressed individually in the nematode epidermis. One is able to interfere with diverse aspects of host cell biology, altering vesicle trafficking and preventing the key STAT-like transcription factor STA-2 from activating defensive antimicrobial peptide gene expression. The second, potentially as a consequence of a host surveillance mechanism, increases STA-2 levels in the nucleus, modifies the nucleolus, and causes increased defence gene expression. Our results highlight the remarkably complex and potentially antagonistic mechanisms that come into play in the interaction between co-evolved hosts and pathogens.Competing Interest StatementThe authors have declared no competing interest.