Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration

Williamson, Angela L., Lustigman, Sara, Oksov, Yelena, Deumic, Vehid, Plieskatt, Jordan, Mendez, Susana, Zhan, Bin, Bottazzi, Maria Elena, Hotez, Peter J. and Loukas, Alex (2006) Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration. Infection and Immunity, 74 2: 961-967.


Author Williamson, Angela L.
Lustigman, Sara
Oksov, Yelena
Deumic, Vehid
Plieskatt, Jordan
Mendez, Susana
Zhan, Bin
Bottazzi, Maria Elena
Hotez, Peter J.
Loukas, Alex
Title Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration
Formatted title Ancylostoma caninum MTP-1, an astacin-like metalloprotease secreted by infective hookworm larvae, is involved in tissue migration
Journal name Infection and Immunity   Check publisher's open access policy
ISSN 0019-9567
1070-6313
1098-5522
Publication date 2006-02
Sub-type Article (original research)
DOI 10.1128/IAI.74.2.961-967.2006
Volume 74
Issue 2
Start page 961
End page 967
Total pages 7
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Formatted abstract Infective larvae (L3) of nematodes secrete macromolecules that are critical to infection and establishment of the parasite in the host. The dog hookworm Ancylostoma caninum secretes an astacin-like metalloprotease, Ac-MTP-1, upon activation in vitro with host serum. Recombinant Ac-MTP-1 was expressed in the baculovirus/insect cell system as a secreted protein and was purified from culture medium by two separate methods, cation-exchange fast-performance liquid chromatography and gelatin-affinity chromatography. Recombinant MTP-1 was catalytically active and digested a range of native and denatured connective tissue substrates, including gelatin, collagen, laminin, and fibronectin. A dog was immunized with recombinant Ac-MTP-1 formulated with AS03 adjuvant, and the antiserum was used to immunolocalize the anatomic sites of expression within A. caninum L3 to secretory granules in the glandular esophagus and the channels that connect the esophagus to the L3 surface and to the cuticle. Antiserum inhibited the ability of recombinant MTP-1 to digest collagen by 85% and inhibited larval migration through tissue in vitro by 70 to 75%, in contrast to just 5 to 10% inhibition obtained with preimmunization serum. The metalloprotease inhibitors EDTA and 1,10-phenanthroline also reduced the penetration of L3 through skin in vitro by 43 to 61%. The data strongly suggest that Ac-MTP-1 is critical for the invasion process of hookworm larvae, and moreover, that antibodies against the enzyme can neutralize its function and inhibit migration.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
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