The Molecular Biology of Drug Resistance in Parasitic Helminths

  • Gerald C. Coles

Abstract

Biochemical and molecular biological studies have been conducted on drug or pesticide resistance in bacteria, cancer cells, fungi, insects, plants and protozoa and indicate that the major mechanisms of resistance are reduced drug uptake, increased drug inactivation and altered receptor sites or sometimes a combination of these mechanisms. By contrast very little is known about the occurrence, importance or drug resistant mechanisms in parasitic helminths. A prerequisite for biochemical studies is the isolation and selection of highly resistant strains of worms, which requires extensive field work and simplified detection and selection procedures. From these studies a range of nematodes and trematodes resistant to existing anthelmintics are likely to arise.

Comparison of resistant and susceptible strains of single species will explain the biochemical mechanisms of resistance and possibly the exact mechanism of action of the anthelmintic. If resistance involves altered receptor or effector site, DNA sequencing of the receptor site should indicate which changes in amino acid sequence would result in a loss of drug binding. Apart from explaining host parasite differences in drug response, knowlege of resistance mechanisms may possibly lead to their being overcome by chemical means, and might provide probes for detecting resistance in the field. Since resistance mechanisms may not be identical in all isolates of the same species, probes may also rapidly indicate mechanisms of resistance in field isolates. Currently benzimidazole and levamisole resistant ovine nematodes and oxamniquine resistant Schistosoma mansoni could be examined by these techniques.

An alternative method of finding exploitable differences between host and parasite is to determine mechanisms of action of novel types of compounds which show good anthelmintic activity but have not proved suitable for commercial development. Artifically produced (mutated) strains or in vitro selected field strains may yield drug resistant worms which could be of value in determining the mechanism of action and showing further host parasite biochemical differences. These diffrences cuold then be used as the basis for in vitro screen for novel chemicals

Keywords

Drug Resistance Resistant Strain Insecticide Resistance Schistosoma Mansoni Parasitic Helminth 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Chapman and Hall 1989

Authors and Affiliations

  • Gerald C. Coles
    • 1
  1. 1.Department of ZoologyUniversity of MassachusettsAmherstUSA

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