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Infect Immun. 1990 Dec; 58(12): 3883–3892.
PMCID: PMC313750

Metalloproteases of infective Ancylostoma hookworm larvae and their possible functions in tissue invasion and ecdysis.


To infect their hosts, hookworm larvae must exsheath and migrate through connective tissue. A modified in vitro skin chamber was used to show that the human hookworm Ancylostoma duodenale and the zoonotic canine hookworm Ancylostoma caninum penetrate epidermis, basement membrane, and dermis in similar ways. These similarities in tissue invasion properties reflect the observed biochemical similarities in parasite protease composition. The larvae of both species contain protease activity that is inhibited by o-phenanthroline; this identifies the proteases as metalloproteases. The enzyme activities exhibit an alkaline pH optimum between pH 9 and 10. During modified sodium dodecyl sulfate-polyacrylamide gel electrophoresis in which a protein substrate (either casein or gelatin) was used, the protease activities resolved into a major band at an Mr of 68,000 and a minor band at an Mr of 38,000. Proteases were released by living A. caninum larvae in vitro and degraded purified and radiolabeled casein to smaller peptides. Motile hookworm larvae were also incubated with purified and radiolabeled connective tissue macromolecules in vitro. Both Ancylostoma species degraded human fibronectin to a 60,000-Mr polypeptide intermediate, but could not degrade solubilized bovine elastin or human laminin. In contrast, the obligate skin-penetrating nematode Strongyloides stercoralis degraded all three substrates. This biochemical difference may explain some observed differences in invasiveness.

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  • BEAVER PC. Larva migrans. Exp Parasitol. 1956 Nov;5(6):587–621. [PubMed]
  • Beaver PC. The nature of visceral larva migrans. J Parasitol. 1969 Feb;55(1):3–12. [PubMed]
  • Croese TJ. Eosinophilic enteritis--a recent north Queensland experience. Aust N Z J Med. 1988 Dec;18(7):848–853. [PubMed]
  • Dresden MH, Rege AA, Murrell KD. Strongyloides ransomi: proteolytic enzymes from larvae. Exp Parasitol. 1985 Apr;59(2):257–263. [PubMed]
  • Fraker PJ, Speck JC., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. [PubMed]
  • Franz TJ. Percutaneous absorption on the relevance of in vitro data. J Invest Dermatol. 1975 Mar;64(3):190–195. [PubMed]
  • Gamble HR, Lichtenfels JR, Purcell JP. Light and scanning electron microscopy of the ecdysis of Haemonchus contortus infective larvae. J Parasitol. 1989 Apr;75(2):303–307. [PubMed]
  • Gamble HR, Purcell JP, Fetterer RH. Purification of a 44 kilodalton protease which mediates the ecdysis of infective Haemonchus contortus larvae. Mol Biochem Parasitol. 1989 Feb;33(1):49–58. [PubMed]
  • Granelli-Piperno A, Reich E. A study of proteases and protease-inhibitor complexes in biological fluids. J Exp Med. 1978 Jul 1;148(1):223–234. [PMC free article] [PubMed]
  • Hawdon JM, Schad GA. Serum-stimulated feeding in vitro by third-stage infective larvae of the canine hookworm Ancylostoma caninum. J Parasitol. 1990 Jun;76(3):394–398. [PubMed]
  • Hotez PJ. Hookworm disease in children. Pediatr Infect Dis J. 1989 Aug;8(8):516–520. [PubMed]
  • Hotez PJ, Cerami A. Secretion of a proteolytic anticoagulant by Ancylostoma hookworms. J Exp Med. 1983 May 1;157(5):1594–1603. [PMC free article] [PubMed]
  • Hotez PJ, Trang NL, McKerrow JH, Cerami A. Isolation and characterization of a proteolytic enzyme from the adult hookworm Ancylostoma caninum. J Biol Chem. 1985 Jun 25;260(12):7343–7348. [PubMed]
  • KALMON EH. Creeping eruption associated with transient pulmonary infiltrations. Radiology. 1954 Feb;62(2):222–226. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [PubMed]
  • Leiby DA, el Naggar HM, Schad GA. Thirty generations of Ancylostoma duodenale in laboratory-reared beagles. J Parasitol. 1987 Aug;73(4):844–848. [PubMed]
  • Lepage T, Gache C. Purification and characterization of the sea urchin embryo hatching enzyme. J Biol Chem. 1989 Mar 25;264(9):4787–4793. [PubMed]
  • LEE CL, LEWERT RM. Quantitative studies of the collagenase-like enzymes of cercariae of Schistosoma mansoni and the larvae of Strongyloides ratti. J Infect Dis. 1956 Jul-Aug;99(1):1–14. [PubMed]
  • Liotta LA, Rao CN, Wewer UM. Biochemical interactions of tumor cells with the basement membrane. Annu Rev Biochem. 1986;55:1037–1057. [PubMed]
  • Little MD, Halsey NA, Cline BL, Katz SP. Ancylostoma larva in a muscle fiber of man following cutaneous larva migrans. Am J Trop Med Hyg. 1983 Nov;32(6):1285–1288. [PubMed]
  • Matthews BE. Invasion of skin by larvae of the cat hookworm, Ancylostoma tubaeforme. Parasitology. 1972 Dec;65(3):457–467. [PubMed]
  • Matthews BE. Mechanism of skin penetration by Ancylostoma tubaeforme larvae. Parasitology. 1975 Feb;70(1):25–38. [PubMed]
  • Matthews BE. Skin penetration by Necator americanus larvae. Z Parasitenkd. 1982;68(1):81–86. [PubMed]
  • McKerrow JH. Parasite proteases. Exp Parasitol. 1989 Jan;68(1):111–115. [PubMed]
  • McKerrow JH, Brindley P, Brown M, Gam AA, Staunton C, Neva FA. Strongyloides stercoralis: identification of a protease that facilitates penetration of skin by the infective larvae. Exp Parasitol. 1990 Feb;70(2):134–143. [PubMed]
  • McKerrow JH, Pino-Heiss S, Lindquist R, Werb Z. Purification and characterization of an elastinolytic proteinase secreted by cercariae of Schistosoma mansoni. J Biol Chem. 1985 Mar 25;260(6):3703–3707. [PubMed]
  • Miller TA. Hookworm infection in man. Adv Parasitol. 1979;17:315–384. [PubMed]
  • Molla A, Tanase S, Hong YM, Maeda H. Interdomain cleavage of plasma fibronectin by zinc-metalloproteinase from Serratia marcescens. Biochim Biophys Acta. 1988 Jun 29;955(1):77–85. [PubMed]
  • MUHLEISEN JP. Demonstration of pulmonary migration of the causative organism of creeping eruption. Ann Intern Med. 1953 Mar;38(3):595–600. [PubMed]
  • Norris DE. The migratory behavior of the infective-stage larvae of Ancylostoma braziliense and Ancylostoma tubaeforme in rodent paratenic hosts. J Parasitol. 1971 Oct;57(5):998–1009. [PubMed]
  • Schad GA. Ancylostoma duodenale: maintenance through six generations in helminth-native pups. Exp Parasitol. 1979 Apr;47(2):246–253. [PubMed]
  • Schad GA, Hellman ME, Muncey DW. Strongyloides stercoralis: hyperinfection in immunosuppressed dogs. Exp Parasitol. 1984 Jun;57(3):287–296. [PubMed]
  • Ossowski L, Unkeless JC, Tobia A, Quigley JP, Rifkin DB, Reich E. An enzymatic function associated with transformation of fibroblasts by oncogenic viruses. II. Mammalian fibroblast cultures transformed by DNA and RNA tumor viruses. J Exp Med. 1973 Jan 1;137(1):112–126. [PMC free article] [PubMed]

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