Molecular Characterization ofAncylostoma ceylanicumKunitz-Type Serine Protease Inhibitor: Evidence for a Role in Hookworm-Associated Growth Delay

• DOI: 10.1128/iai.72.4.2214-2221.2004
• Publication Date: 2004-03-23T22:43:10Z
• Authors: Daniel Chu; Richard D. Bungiro; Maureen Ibanez; Lisa M. Harrison; Eva Campodonico; Brian F. Jones; Juliusz Mieszczanek; Petr Kuzmic; Michael Cappello
• Keywords: Hookworm Infections; Ancylostoma; Ancylostomiasis; Ancylostoma duodenale; Hookworm Infections

ABSTRACT Hookworm infection is a major cause of iron deficiency anemia and malnutrition in developing countries. The Ancylostoma ceylanicum Kunitz-type inhibitor (AceKI) 7.9-kDa broad-spectrum trypsin, chymotrypsin, pancreatic elastase that has previously been isolated from adult hookworms. Site-directed mutagenesis the predicted P1 inhibitory reactive site amino acid confirmed role Met 26 mediating inhibition three target serine proteases. By using reverse transcription-PCR, it was demonstrated level AceKI gene expression increased following activation third-stage larvae with serum highest reached stage parasite. Immunohistochemistry studies performed polyclonal immunoglobulin G raised against recombinant showed localized to subcuticle hookworm, suggesting potential vivo neutralizing intestinal proteases at surface Immunization shown confer partial protection hookworm-associated growth delay without measurable effect on anemia. Taken together, data suggest plays pathogenesis delay, perhaps through nutrient absorption infected hosts.