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Antimicrobial Agents and Chemotherapy, November 2008, p. 3980-3986, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00523-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Phenotypic Characterization of Two Ancylostoma caninum Isolates with Different Susceptibilities to the Anthelmintic Pyrantel{triangledown}

Steven R. Kopp,1 Glen T. Coleman,1 James S. McCarthy,2 and Andrew C. Kotze3*

School of Veterinary Science, University of Queensland,1 Australian Centre for Tropical and International Health, a Joint Program of the Queensland Institute for Medical Research and the University of Queensland,2 CSIRO Livestock Industries, Brisbane, Australia3

Received 22 April 2008/ Returned for modification 6 July 2008/ Accepted 6 August 2008

The anthelmintic pyrantel plays an important role in the control of gastrointestinal helminths of humans and domestic animals. Despite the demonstration of pyrantel resistance in several helminth species over the last 20 years, the resistance mechanism remains unclear. It has been hypothesized that resistance may arise as a consequence of changes to the relative proportions of subpopulations of nicotinic acetylcholine receptors (nAchRs). To test this hypothesis, we examined the responses of two isolates of the canine hookworm Ancylostoma caninum with low-level resistance (isolate NT) and high-level resistance (isolate PR) to pyrantel to nicotinic agonist drugs reported to be selective for three nAchR subtypes. We used larval motility and conformation assays and force transduction experiments with adult worms. Pyrantel and levamisole were less potent against larvae of isolate PR than larvae of isolate NT (up to an 18-fold increase in the 50% inhibitory concentration); on the other hand, bephenium was more potent against larvae of isolate PR than larvae of isolate NT (twofold) and nicotine had the same potency against larvae of both isolates. In adults, pyrantel, levamisole, and nicotine were less potent against isolate PR than isolate NT (two- to threefold), but the potency of bephenium against the two isolates was equivalent. Our data indicate a complex pattern of nAchRs in this species and suggest that the two isolates differ in their relative sensitivities to agonists targeting different nAchRs.

* Corresponding author. Mailing address: CSIRO Livestock Industries, 306 Carmody Rd., St. Lucia, Brisbane QLD 4067, Australia. Phone: 61 7 3214 2355. Fax: 61 7 3214 2900. E-mail: andrew.kotze{at}csiro.au

{triangledown} Published ahead of print on 18 August 2008.

Antimicrobial Agents and Chemotherapy, November 2008, p. 3980-3986, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00523-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kotze, A. C., Lowe, A., O'Grady, J., Kopp, S. R., Behnke, J. M. (2009). Dose-Response Assay Templates for In vitro Assessment of Resistance to Benzimidazole and Nicotinic Acetylcholine Receptor Agonist Drugs in Human Hookworms. Am J Trop Med Hyg 81: 163-170 [Abstract] [Full Text]  


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