Hookworm aspartic protease, Na-APR-2, cleaves human hemoglobin and serum proteins in a host-specific fashion.
Hookworms are voracious blood-feeders. The cloning and functional expression of an aspartic protease, Na-APR-2, from the human hookworm Necator americanus are described here. Na-APR-2 is more similar to a family of nematode-specific, aspartic proteases than it is to cathepsin D or pepsin, and the term "nemepsins" for members of this family of nematode-specific hydrolases is proposed. Na-apr-2 mRNA was detected in blood-feeding, developmental stages only of N. americanus, and the protease was expressed in the intestinal lumen, amphids, and excretory glands. Recombinant Na-APR-2 cleaved human hemoglobin (Hb) and serum proteins almost twice as efficiently as the orthologous substrates from the nonpermissive dog host. Moreover, only 25% of the Na-APR-2 cleavage sites within human Hb were shared with those generated by the related N. americanus cathepsin D, Na-APR-1. Antiserum against Na-APR-2 inhibited migration of 50% of third-stage N. americanus larvae through skin, which suggests that aspartic proteases might be effective vaccines against human hookworm disease.
Williamson
Angela L
AL
Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, Queensland, Australia.
Brindley
Paul J
PJ
Abbenante
Giovanni
G
Datu
Bennett J D
BJ
Prociv
Paul
P
Berry
Colin
C
Girdwood
Karen
K
Pritchard
David I
DI
Fairlie
David P
DP
Hotez
Peter J
PJ
Zhan
Bin
B
Loukas
Alex
A
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001798:Blood Proteins / Q000378:metabolism*; D004285:Dogs; D020869:Gene Expression Profiling; D006454:Hemoglobins / Q000378:metabolism*; D006790:Host-Parasite Interactions; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism; D008969:Molecular Sequence Data; D017221:Necator americanus / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013379:Substrate Specificity; D013997:Time Factors
D001798:Blood Proteins; D006454:Hemoglobins; D016282:Aspartic Acid Endopeptidases