The hemoglobins of the trematodes Fasciola hepatica and Paramphistomum epiclitum: A molecular biological, physico‐chemical, kinetic, and vaccination study

Abstract

The trematode Fasciola hepatica (Fa.he.) is a common parasite of human and livestock. The hemoglobin (Hb) of Fa.he., a potential immunogen, was chosen for characterization in the search for an effective vaccine. Characterization of trematode Hbs show that they are intracellular single-domain globins with the following remarkable features: (1) Fa.he. expresses two Hb isoforms that differ at two amino acid sites (F1: 119Y/123Q; F2: 119F/123L). Both isoforms are monoacetylated at their N-termini; (2) the genes coding for Fa.he. and Paramphistomum epiclitum (Pa.ep.) Hbs are interrupted by two introns at the conserved positions B12.2 and G7.0.; (3) UV/VIS and resonance Raman spectroscopy identify the recombinant Fa.he. HbF2 as a pentacoordinated high-spin ferrous Hb; (4) electron paramagnetic resonance spectroscopy of cyano-met Fa.he. HbF2 proves that the endogenously bound imidazole has no imidazolate character; (5) the major structural determinants of the globin fold are present, they contain a TyrB10/TyrE7 residue pair on the distal side. Although such distal-site pair is a signature for high oxygen affinity, as shown for Pa.ep. Hb, the oxygen-binding rate parameters for Fa.he. Hb are intermediate between those of myoglobin and those of other trematode Hbs; (6) the threedimensional structure of recombinant Fa.he. HbF2 from this study closely resembles the threedimensional structure of Pa.ep. determined earlier. The set of distal-site polar interactions observed in Pa.ep. Hb is matched with small but significant structural adjustments; (7) despite the potential immunogenic character of the fluke Hb, vaccination of calves with recombinant Fa.he. HbF2 failed to promote protection against parasitic infection.

Recognition Pattern of the Fasciola hepatica Excretome/Secretome during the Course of an Experimental Infection in Sheep by 2D Immunoproteomics

“…These parasites usually live in semi-anaerobic environments, so extracellular globins may have biological functions beyond oxygen transport and storage. Among them, oxygen scavenging, heme reserve for egg production, and nitric oxide dioxygenase have been postulated [42].…”

Fasciola hepatica and Schistosoma mansoni: Identification of Common Proteins by Comparative Proteomic Analysis

“…Among these, hemoglobin-like proteins have been identified (Dalton et al, 1996). The ES proteins, including Hbs, are potent antigens that are potentially useful in eliciting host immunological resistance against the parasitic infection through vaccination (Dewilde et al, 2008). A vaccine trial in cattle with Hb resulted in a 43.8% protection level against fluke infection (Dalton et al, 1996).…”

Chronic Wasting Due to Liver and Rumen Flukes in Sheep

“…Since diagnosis of rumen flukes is difficult during the phase when severe symptoms can occur, vaccination would be a valuable approach to avoid such severe cases. However, little has been done in this direction except for a single study in which a recombinant Paramphistomum epiclitum haemoglobin has been used to vaccinate calves, however, no protective effect was observed [ 112 ].…”