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Collagen-enriched cuticle forms the outermost layer of skin in nematode Caenorhabditis elegans. The nematode's genome encodes 177 collagens, but little is known about their role in maintaining the structure or barrier function of the cuticle. In this study, we found six permeability determining (PD) collagens. Loss of any of these PD collagens-DPY-2, DPY-3, DPY-7, DPY-8, DPY-9, and DPY-10-led to enhanced susceptibility of nematodes to paraquat (PQ) and antihelminthic drugs- levamisole and ivermectin. Upon exposure to PQ, PD collagen mut