The cysteine-rich virulence factor NipA of Arthrobotrys flagrans interferes with cuticle integrity of Caenorhabditis elegans

Jennifer Emser, Nicole Wernet, Birgit Hetzer, Elke Wohlmann and Reinhard Fischer ()
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Jennifer Emser: Karlsruhe Institute of Technology (KIT) - South Campus
Nicole Wernet: Karlsruhe Institute of Technology (KIT) - South Campus
Birgit Hetzer: Max Rubner-Institut (MRI) - Federal Research Institute of Nutrition and Food
Elke Wohlmann: Karlsruhe Institute of Technology (KIT) - South Campus
Reinhard Fischer: Karlsruhe Institute of Technology (KIT) - South Campus

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract Animals protect themself from microbial attacks by robust skins or a cuticle as in Caenorhabditis elegans. Nematode-trapping fungi, like Arthrobotrys flagrans, overcome the cuticle barrier and colonize the nematode body. While lytic enzymes are important for infection, small-secreted proteins (SSPs) without enzymatic activity, emerge as crucial virulence factors. Here, we characterized NipA (nematode induced protein) which A. flagrans secretes at the penetration site. In the absence of NipA, A. flagrans required more time to penetrate C. elegans. Heterologous expression of the fungal protein in the epidermis of C. elegans led to blister formation. NipA contains 13 cysteines, 12 of which are likely to form disulfide bridges, and the remaining cysteine was crucial for blister formation. We hypothesize that NipA interferes with cuticle integrity to facilitate fungal entry. Genome-wide expression analyses of C. elegans expressing NipA revealed mis-regulation of genes associated with extracellular matrix (ECM) maintenance and innate immunity.

Date: 2024
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DOI: 10.1038/s41467-024-50096-4

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