Characterisation of tetraspanins from Schistosoma haematobium and evaluation of their potential as novel diagnostic markers

Mekonnen, Gebeyaw G., Tedla, Bemnet A., Pearson, Mark S., Becker, Luke, Field, Matt, Amoah, Abena S., van Dam, Govert, Corstjens, Paul L.A.M., Mduluza, Takafira, Mutapi, Francisca, Loukas, Alex, and Sotillo, Javier (2022) Characterisation of tetraspanins from Schistosoma haematobium and evaluation of their potential as novel diagnostic markers. PLoS Neglected Tropical Diseases, 16 (1). e0010151.

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Abstract

Schistosoma haematobium is the leading cause of urogenital schistosomiasis and it is recognised as a class 1 carcinogen due to the robust association of infection with bladder cancer. In schistosomes, tetraspanins (TSPs) are abundantly present in different parasite proteomes and could be potential diagnostic candidates due to their accessibility to the host immune system. The large extracellular loops of six TSPs from the secretome (including the soluble excretory/secretory products, tegument and extracellular vesicles) of S. haematobium (Sh-TSP-2, Sh-TSP-4, Sh-TSP-5, Sh-TSP-6, Sh-TSP-18 and Sh-TSP-23) were expressed in a bacterial expression system and polyclonal antibodies were raised to the recombinant proteins to confirm the anatomical sites of expression within the parasite. Sh-TSP-2, and Sh-TSP-18 were identified on the tegument, whereas Sh-TSP-4, Sh-TSP-5, Sh-TSP-6 and Sh-TSP-23 were identified both on the tegument and internal tissues of adult parasites. The mRNAs encoding these TSPs were differentially expressed throughout all schistosome developmental stages tested. The potential diagnostic value of three of these Sh-TSPs was assessed using the urine of individuals (stratified by infection intensity) from an endemic area of Zimbabwe. The three Sh-TSPs were the targets of urine IgG responses in all cohorts, including individuals with very low levels of infection (those positive for circulating anodic antigen but negative for eggs by microscopy). This study provides new antigen candidates to immunologically diagnose S. haematobium infection, and the work presented here provides compelling evidence for the use of a biomarker signature to enhance the diagnostic capability of these tetraspanin.

Item ID: 72412
Item Type: Article (Research - C1)
ISSN: 1935-2735
Copyright Information: © 2022 Mekonnen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funders: National Health and Medical Research Council (NHMRC)
Projects and Grants: NHMRC APP1037304, NHMRC APP1117504
Date Deposited: 23 Feb 2022 23:21
FoR Codes: 31 BIOLOGICAL SCIENCES > 3102 Bioinformatics and computational biology > 310204 Genomics and transcriptomics @ 50%
31 BIOLOGICAL SCIENCES > 3104 Evolutionary biology > 310407 Host-parasite interactions @ 50%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200101 Diagnosis of human diseases and conditions @ 100%
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