engleski

Interpreting cathepsin proteases from transcriptome of Anisakis pegreffii

Anisakis pegreffii is a nematode that parasitizes marine cetaceans as definitive hosts, accidentally infecting humans for a limited time span. Although the knowledge of disease mediators during anisakiasis in humans is incomprehensive, we can close the gaps by applying what is known from other helminth infections. Cathepsins are key virulence factors in disease progression and synchronized expression of these proteolytic enzymes is considered a hallmark of parasitosis. Figuring as potential disease biomarkers, they are also important subjects in drug or vaccine targets investigation. The functional insights of these proteases vary during life cycle of parasites in context of infection type, eclosion, feeding and immune evasion. Cathepsins are clusters of proteolytic enzymes of lysosomal origin divided into three classes – cysteine, serine and aspartic proteases. Cysteine cathepsins occur in multiple forms as cathepsin B-like (B, O, C, and X or Z), cathepsin L-like (L, V, K, S, and H), cathepsin F-like (W and F), and placenta-specific cathepsins (cathepsins J/P, M, Q, R, 3, 6, 7 and 8) that are exclusively expressed in rat/mouse placenta. Biochemically, cathepsins A and G have been distinguished as serine proteases, whereas D and E belong to aspartic endopeptidases. Through in silico data-mining of A. pegreffii infective third-stage larvae (L3) transcriptomes, we have identified multiple signatures of cathepsin A carboxypeptidases and cathepsin D. Apart from these, L3 express a vast array of cysteine proteases. In addition to cathepsin B, F and L, the presence of putative cathepsin Z and W has also been validated. A. pegreffii presents at least four distinct clades of cathepsin B and L proteolytic enzymes, and a unique cathepsin F having 51% identity to human orthologue. In general, A. pegreffii cysteine cathepsin orthologues share maximum identity to Toxocara canis rather than free-living model Caenorhabditis elegans. Putative A. pegreffii cathepsin B1 has duplet histidine conserved in occluding loop, thus suggesting both effective exopeptidase and endopeptidase activities on specific substrates. Interestingly, the three other putative cathepsin B clades (B2, B3, B4) show to be non-canonical, expressing shorter occluding loops. Such atypical proteases could open interesting dimensions in understanding nematode biology and scoping for drug discovery.

Anisakis pegreffii ; proteases ; cathepsins ; transcriptomics

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