Cleavage of hemoglobin by hookworm cathepsin D aspartic proteases and its potential contribution to host specificity.
Hookworms routinely reach the gut of nonpermissive hosts but fail to successfully feed, develop, and reproduce. To investigate the effects of host-parasite coevolution on the ability of hookworms to feed in nonpermissive hosts, we cloned and expressed aspartic proteases from canine and human hookworms. We show here that a cathepsin D-like protease from the canine hookworm Ancylosotoma caninum (Ac-APR-1) and the orthologous protease from the human hookworm Necator americanus (Na-APR-1) are expressed in the gut and probably exert their proteolytic activity extracellularly. Both proteases were detected immunologically and enzymatically in somatic extracts of adult worms. The two proteases were expressed in baculovirus, and both cleaved human and dog hemoglobin (Hb) in vitro. Each protease digested Hb from its permissive host between twofold (whole molecule) and sixfold (synthetic peptides) more efficiently than Hb from the nonpermissive host, despite the two proteases' having identical residues lining their active site clefts. Furthermore, both proteases cleaved Hb at numerous distinct sites and showed different substrate preferences. The findings suggest that the paradigm of matching the molecular structure of the food source within a host to the molecular structure of the catabolic proteases of the parasite is an important contributing factor for host-parasite compatibility and host species range.
Williamson
Angela L
AL
Division of Infectious Diseases and Immunology, Queensland Institute of Medical Research, QLD, Australia.
Brindley
Paul J
PJ
Abbenante
Giovanni
G
Prociv
Paul
P
Berry
Colin
C
Girdwood
Karen
K
Pritchard
David I
DI
Fairlie
David P
DP
Hotez
Peter J
PJ
Dalton
John P
JP
Loukas
Alex
A
D000723:Ancylostomatoidea / Q000201:enzymology*; D000818:Animals; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D004064:Digestive System / Q000201:enzymology; D004285:Dogs; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006790:Host-Parasite Interactions; D006801:Humans; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry; D011994:Recombinant Proteins / Q000378:metabolism; D013045:Species Specificity; D013379:Substrate Specificity
D006454:Hemoglobins; D010455:Peptides; D011994:Recombinant Proteins; D002402:Cathepsin D