Glyceraldehyde‐3‐phosphate dehydrogenase of the parasitic nematode Haemonchus contortus binds to complement C3 and inhibits its activity

Abstract

Haemonchus contortus is an economically important gastrointestinal parasite that infects primarily sheep and goats. To survive inside the host, the parasite must overcome the host immune response. In this study, we have identified and characterized a complement-C3-binding protein (H.c-C3BP) from this parasite employing biochemical and molecular biology tools. Initially, a truncated form of the protein was isolated from the excretory-secretory products of the parasite using C3-Sepharose column that facilitated its identification by mass spectroscopy. Subsequently, the parent molecule was generated in E. coli, and sequence analysis confirmed it as glyceraldehyde-3-phosphate dehydrogenase (GAPDH). GAPDH reacted with the antiserum raised against the truncated protein, and the truncated protein reacted with anti-GAPDH antiserum. The protein inhibited complement function as measured by haemolytic assay and membrane attack complex (MAC) formation. Sera from H. contortus-infected animals reacted with GAPDH as well as the truncated form of the protein, which further lend support to protein secretion. Thus, the C3-binding property of H. contortus GAPDH is a new function, and it represents a new entity of complement-binding protein. Identification and characterization of H.c-C3BP should facilitate development of new therapeutics considering a key role of this protein in immune modulation.

Excretory/secretory proteome of 14-day schistosomula, Schistosoma japonicum

“…Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) binds to plasminogen, thereby facilitating the invasion and migration of schistosomes into the host [47], a process that is related to anticoagulation. GAPDH, which is present among the ES products of Haemonchus contortus, is a complement-C3-binding protein that can protect worms from immune attack by inhibiting complement activity [48]. The expression of IgG antibodies specific for GAPDH is correlated with resistance to schistosome infection, suggesting the potential of GAPDH as vaccine candidates [49].…”

Cryptococcus Strains with Different Pathogenic Potentials Have Diverse Protein Secretomes

“…C. neoformans enolase has been implicated in plasminogen activation, allowing Cryptococcus strains to traverse endothelial cells and potentially cross the bloodbrain barrier (BBB) (43,44). Extracellular GAPDH appears to have different roles in the progression of infection by a wide range of pathogens, including plasminogen binding in parasites (45), adherence to host cells by pathogenic Escherichia coli, Neisseria meningitides, Bacillus anthracis, Paracoccidioides brasiliensis, and Candida albicans (33), and complement and fibronectin binding in helminths (46,47) and as an immunogen in C. albicans (26). Given these diverse roles, cryptococcal GAPDH secreted by the C. gattii VGIIb strain has the potential to trigger a host response leading to clearance from the lung or to aid disease progression, leading to cryptococcal meningitis.…”

DNA vaccine encoding the moonlighting protein Onchocerca volvulus glyceraldehyde-3-phosphate dehydrogenase ( Ov -GAPDH) leads to partial protection in a mouse model of human filariasis

“…González-Miguel et al found GAPDH on the surface and in the excretory/secretory (ES) antigens of Dirofilaria immitis [14]. Its plasminogen-binding activity [9] suggests a role in host invasion and binding of complement molecules by helminth GAPDH protects the parasitic nematode Haemonchus contortus from complement attack [15]. This leads to the assumption that a GAPDH vaccine may target multiple physiological reactions of the parasite.…”