An atypical and functionally diverse family of Kunitz-type cysteine/serine proteinase inhibitors secreted by the helminth parasite Fasciola hepatica.
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2020-11-26Author
Smith, David
Cwiklinski, Krystyna
Jewhurst, Heather
Tikhonova, Irina G.
Dalton, John P.
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Smith, David, Cwiklinski, Krystyna, Jewhurst, Heather, Tikhonova, Irina G., & Dalton, John P. (2020). An atypical and functionally diverse family of Kunitz-type cysteine/serine proteinase inhibitors secreted by the helminth parasite Fasciola hepatica. Scientific Reports, 10(1), 20657. doi:10.1038/s41598-020-77687-7
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Abstract
Fasciola hepatica is a global parasite of humans and their livestock. Regulation of parasite-secreted cathepsin L-like cysteine proteases associated with virulence is important to fine-tune parasite-host interaction. We uncovered a family of seven Kunitz-type (FhKT) inhibitors dispersed into five phylogenetic groups. The most highly expressed FhKT genes (group FhKT1) are secreted by the newly excysted juveniles (NEJs), the stage responsible for host infection. The FhKT1 inhibitors do not inhibit serine proteases but are potent inhibitors of parasite cathepsins L and host lysosomal cathepsin L, S and K cysteine proteases (inhibition constants¿