Trichuris trichiura egg extract proteome reveals potential diagnostic targets and immunomodulators

Abstract

Embryonated eggs are the infectious developmental stage of Trichuris trichiura and are the primary stimulus for the immune system of the definitive host. The intestinal-dwelling T. trichiura affects an estimated 465 million people worldwide with an estimated global burden of disease of 640 000 DALYs (Disability Adjusted Life Years). In Latin America and the Caribbean, trichuriasis is the most prevalent soil transmitted helminthiasis in the region (12.3%; 95% CI). The adverse health consequences impair childhood school performance and reduce school attendance resulting in lower future wage-earning capacity. The accumulation of the long-term effects translates into poverty promoting sequelae and a cycle of impoverishment. Each infective T. trichiura egg carries the antigens needed to face the immune system with a wide variety of proteins present in the shell, larvae’s surface, and the accompanying fluid that contains their excretions/secretions. We used a proteomic approach with tandem mass spectrometry to investigate the proteome of soluble non-embryonated egg extracts of T. trichiura obtained from naturally infected African green monkeys (Chlorocebus sabaeus). A total of 231 proteins were identified, 168 of them with known molecular functions. The proteome revealed common proteins families which are known to play roles in energy and metabolism; the cytoskeleton, muscle and motility; proteolysis; signaling; the stress response and detoxification; transcription and translation; and lipid binding and transport. In addition to the study of the T. trichiura non-embryonated egg proteome, the antigenic profile of the T. trichiura non-embryonated egg and female soluble proteins against serum antibodies from C. sabaeus naturally infected with trichuriasis was investigated. We used an immunoproteomic approach by Western blot and tandem mass spectrometry from the corresponding SDS-PAGE gels. Vitellogenin N and VWD and DUF1943 domain containing protein, poly-cysteine and histidine tailed protein isoform 2, heat shock protein 70, glyceraldehyde-3-phosphate dehydrogenase, actin, and enolase, were among the potential immunoactive proteins. To our knowledge, this is the first study on the T. trichiura non-embryonated egg proteome as a novel source of information on potential targets for immunodiagnostics and immunomodulators from a neglected tropical disease. This initial list of T. trichiura non-embryonated egg proteins (proteome and antigenic profile) can be used in future research on the immunobiology and pathogenesis of human trichuriasis and the treatment of human intestinal immune-related diseases.

Recognition of highly branched N-glycans of the porcine whipworm by the immune system

“…The best match for the proteomic data was to an “uncharacterized” T. suis protein related to a secreted Poly-Cysteine and Histidine-Tailed Metalloprotein from Trichinella spiralis , which is also N-glycosylated ( 33 ) . Homologous proteins, also known as p43, have also been identified in Trichinella pseudospiralis adult secretome ( 34 ) , Trichuris muris excretory-secretory products ( 35 ) and Trichuris trichuria egg and female extracts ( 36 ) . In terms of N-glycomics of the protein band, a typical range of pauci- and oligomannosidic glycans as well as structures carrying LacdiNAc residues with or without phosphorylcholine were revealed upon MALDI-TOF MS/MS of the HPLC-fractionated N-glycans, thereby representing a subset of the overall N-glycome.…”

Identification and profiling of Trichinella spiralis circulating antigens and proteins in sera of mice with trichinellosis

“…spiralis cuticle collagen is up-regulated in muscle larvae at the encapsulated stage compared with its concentration in intestinal infective larvae [ 13 ]. Trichuris trichiura cuticle collagen from egg extract was identified as an antigen reacting with sera of infected African green monkeys [ 24 ]. Identification herein of PX domain protein, enoyl-coA hydratase/isomerase family protein and cuticle collagen as T .…”

Trichuris: A Critical Review

“…Since anthelmintic therapies are generally ineffective, the lack of readily available worms will continue to be a significant barrier to genetic research on Trichuris. The proteome of the non-embryonated eggs of T. trichiura as a unique source of data on prospective targets for immunodiagnostics and immunomodulators from a neglected tropical disease was investigated by Cruz et al and a list of T. trichiura non-embryonated egg proteins (proteome and antigenic profile) was provided which can be used in future research into the pathophysiology and immunobiology of human trichuriasis, as well as the management of disorders of the human intestinal immune system [74]. A number of potential new drugs have been found thanks to the whole-genome sequencing of Trichuris trichiura, which may make worm collection less of a hassle in the future [69].…”