Molecular and functional characterization of a recombinant protein of Trichuris trichiura

Abstract

The pore-forming protein of the human whipworm, Trichuris trichiura, has been postulated to facilitate invasion of the host gut and enable the parasite to maintain its syncytial environment. The data presented here describe the first, to our knowledge, molecular characterization of a pore-forming protein in any helminth and provide a unique demonstration of the functional interaction between a parasite antigen and host molecules. Immunological screening of a T. trichiura cDNA library with T. trichiura infection sera identified a clone of 1.4 kB, the cDNA consisting of 1495 base pairs encoding a protein of 50 kDa. The sequence has a highly repetitive nature containing nine four-disulphide-bonded core domains. Structural prediction analyses reveals an amphipathic nature. TT50 induced pore formation in bilayers in a manner identical to that of the native protein. IgG antibody isolated from T. trichiura infection serum was observed to abolish channel activity.

Characterization of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host–parasite communication

“…Drake et al . characterized a pore-forming protein that T. muris [14] and T. trichiura [13] use to drill holes in the host cell membrane. Furthermore, it has been suggested that a thioredoxin-like protein secreted by the pig whipworm Trichuris suis plays a role in mucosal homeostasis [11].…”

Characterisation of Trichuris muris secreted proteins and extracellular vesicles provides new insights into host-parasite communication

“…Despite this progress, and the tractability of the T. muris model, very few proteomic studies have been conducted, and only a handful of reports have described proteins secreted by Trichuris spp. [9, 10, 11, 12, 13, 14]. Drake et al characterised a pore-forming protein that T. muris [14] and T. trichiura [13] use to drill holes in the host cell membrane.…”

“…[9, 10, 11, 12, 13, 14]. Drake et al characterised a pore-forming protein that T. muris [14] and T. trichiura [13] use to drill holes in the host cell membrane. Furthermore, it has been suggested that a thioredoxin-like protein secreted by the pig whipworm Trichuris suis plays a role in mucosal homeostasis [11].…”

Trichuris muris whey acidic protein induces type 2 protective immunity against whipworm

“…The Tm -WAP gene shares high sequence alignment with the T . trichiura putative porin proteins, TT95 [ 24 ] and TT52 [ 25 ], at 54% and 47% amino acid sequence identity, respectively ( Fig 1B ).…”

“…muris ES are cross-reactive to anti- Tm -WAP49 and anti- Tm -WAP-F8+ Na -GST-1 sera by western blot. Furthermore, Tt 52 and Tt 95 have been described for their ability to generate pores in a planar lipid bilayer [ 12 , 24 , 25 ]. Future studies testing the ability of Tm -WAP antisera to inhibit pore-formation, preventing stichosome penetration and maintenance in the colonic mucosa would be important to fully realize the vaccine potential of WAP.…”