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Distinct characteristics of two intestinal protein compartments discriminated by using fenbendazole and a benzimidazole resistant isolate of Haemonchus contortus
- Source :
- Experimental parasitology. 101(4)
- Publication Year :
- 2003
-
Abstract
- The intestine of Haemonchus contortus is hypersensitive to the effects of the anthelmintic fenbendazole (FBZ). The effects are postulated to stem from disruption of microtubules and interference with apical secretory vesicle transport, followed by release of digestive enzymes into the intestinal cell cytoplasm. Here, FBZ caused marker proteins for both apical (pepsinogen-like protease, PEP-1) and basal (cystatin-like protein) protein compartments to became homogeneously distributed in the cytoplasm of H. contortus intestinal cells. The observations with PEP-1 support the hypothesis that release of hydrolytic enzymes into the intestinal cell cytoplasm contributes to the mechanism of benzimidazole efficacy. A benzimidazole resistant isolate of H. contortus expressed type 1 and 2 intestinal beta-tubulin transcripts that would encode predominantly tyr200 and phe200 variants, respectively. This isolate was resistant to the known intestinal cell alterations induced by FBZ treatment in the susceptible isolate, including inhibition of apical vesicle transport. These results implicate type 1 beta-tubulin in mediating apical vesicle transport in intestinal cells and suggest that the tyr200 variant is a determinant of FBZ resistance in intestinal cells. In contrast, the basal protein compartment demonstrated sensitivity to FBZ treatment in these otherwise "resistant" worms. Hence, distinct FBZ-sensitive components appear to be involved in distributing intestinal proteins into the described apical and basal compartments of normal worms.
- Subjects :
- medicine.medical_treatment
Immunology
Drug Resistance
Microtubule
Antibody Specificity
Tubulin
medicine
Animals
chemistry.chemical_classification
Protease
Sheep
biology
Antinematodal Agents
Immune Sera
Serine Endopeptidases
General Medicine
Fenbendazole
Apical membrane
biology.organism_classification
Secretory Vesicle
Cystatins
Cell biology
Vesicular transport protein
Intestines
Infectious Diseases
Enzyme
chemistry
Biochemistry
Cytoplasm
Parasitology
Benzimidazoles
Haemonchus
Haemonchus contortus
Subjects
Details
- ISSN :
- 00144894
- Volume :
- 101
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Experimental parasitology
- Accession number :
- edsair.doi.dedup.....0a2e81c79160b8957cefd7b0abbda6e1