Drug-efflux and target-site gene expression patterns in Haemonchus contortus larvae able to survive increasing concentrations of levamisole in vitro

Article


Sarai, Ranbir S., Kopp, Steven R., Coleman, Glen T. and Kotze, Andrew C.. 2014. "Drug-efflux and target-site gene expression patterns in Haemonchus contortus larvae able to survive increasing concentrations of levamisole in vitro." International Journal for Parasitology: Drugs and Drug Resistance. 4 (2), pp. 77-84. https://doi.org/10.1016/j.ijpddr.2014.02.001
Article Title

Drug-efflux and target-site gene expression patterns in Haemonchus contortus larvae able to survive increasing concentrations of levamisole in vitro

ERA Journal ID200660
Article CategoryArticle
AuthorsSarai, Ranbir S. (Author), Kopp, Steven R. (Author), Coleman, Glen T. (Author) and Kotze, Andrew C. (Author)
Journal TitleInternational Journal for Parasitology: Drugs and Drug Resistance
Journal Citation4 (2), pp. 77-84
Number of Pages8
Year2014
Place of PublicationUnited Kingdom
ISSN2211-3207
Digital Object Identifier (DOI)https://doi.org/10.1016/j.ijpddr.2014.02.001
Abstract

While there is some evidence that changes in nicotinic acetylcholine receptor (nAChR) subunits confer resistance to levamisole in gastrointestinal helminth parasites, the exact nature of the resistance mechanism(s) is unclear. We utilised the presence of a resistant fraction within the Wallangra 2003 isolate of Haemonchus contortus larvae in order to subdivide the population into three subpopulations of larvae able to survive increasing concentrations of the drug. We then measured gene expression levels in the subpopulations and the larval population as a whole, focusing on genes encoding the subunit components of levamisole-sensitive receptors, genes encoding ancillary proteins involved in receptor assembly, and P-glycoprotein (P-gp) genes. The subpopulation surviving the lowest levamisole concentration showed increases of 1.5- to 3-fold in a number of P-gp genes (Hco-pgp-3, -4, -10, and -14) alongside unchanged receptor genes, compared to the whole Wallangra larval population. On the other hand, the subpopulation surviving the intermediate levamisole concentration showed an increase in only a single P-gp (Hco-pgp-14), alongside decreases in some receptor subunit (Hco-unc-63a) and ancillary protein genes (Hco-unc-50, Hco-ric-3.1 and 3.1). The subpopulation surviving the highest levamisole concentration showed further decreases in receptor subunit genes (Hco-unc-63a and Hco-unc-29 paralogs) as well as genes involved in receptor assembly (Hco-unc-74, Hco-unc-50, Hco-ric-3.1 and 3.1), alongside no increased P-gp gene levels. This suggests a biphasic pattern of drug resistance in the larvae of this worm isolate, in which a non-specific P-gp-mediated mechanism confers low levels of resistance, while higher level resistance is due to altered receptor subunit composition as a result of changes in both subunit composition and in the levels of proteins involved in receptor assembly.

Keywordshaemonchus contortus; levamisole; nicotinic agonists; resistance; microbiology; bacteriology; mycology; parasitology and virology
ANZSRC Field of Research 2020320704. Medical parasitology
Byline AffiliationsCommonwealth Scientific and Industrial Research Organisation (CSIRO), Australia
University of Queensland
Institution of OriginUniversity of Southern Queensland
Permalink -

https://research.usq.edu.au/item/q47wq/drug-efflux-and-target-site-gene-expression-patterns-in-haemonchus-contortus-larvae-able-to-survive-increasing-concentrations-of-levamisole-in-vitro

Download files


Published Version
Coleman_2014_PV.pdf
License: CC BY-NC-ND
File access level: Anyone

  • 825
    total views
  • 129
    total downloads
  • 3
    views this month
  • 1
    downloads this month

Export as

Related outputs

Prevalence of canine heartworm infection in Queensland, Australia: comparison of diagnostic methods and investigation of factors associated with reduction in antigen detection
Constantinoiu, Constantin, Croton, Catriona, Paterson, Mandy B. A., Knott, Lyn, Henning, Joerg, Mallyon, John and Coleman, Glen T.. 2023. "Prevalence of canine heartworm infection in Queensland, Australia: comparison of diagnostic methods and investigation of factors associated with reduction in antigen detection." Parasites and Vectors. 16 (1). https://doi.org/10.1186/s13071-022-05633-9
Identification and prevalence of a gammaherpesvirus in free-ranging northern brown bandicoots (Isoodon macrourus)
Langhorne, Charlotte, Sullivan, Jennifer, Hoy, Julia, Kopp, Steven, Murray, Peter and McMichael, Lee. 2021. "Identification and prevalence of a gammaherpesvirus in free-ranging northern brown bandicoots (Isoodon macrourus)." Journal of Wildlife Disease. 57 (4), pp. 912-916. https://doi.org/10.7589/JWD-D-20-00166
Haematology and serum biochemistry results for anaesthetised northern brown bandicoots (Isoodon macrourus) in south east Queensland
Langhorne, Charlotte, McMichael, Lee, Hoy, Julia, Kopp, Stephen and Murray, Peter. 2021. "Haematology and serum biochemistry results for anaesthetised northern brown bandicoots (Isoodon macrourus) in south east Queensland." Australian Veterinary Journal. 99 (9), pp. 408-411. https://doi.org/10.1111/avj.13098
Clinical pathology of captive endangered mahogany gliders (Petaurus gracilis) in responses to environmental change
McMichael, Lee, Adam, Darlene, Tribe, Andrew, Bynon, Brian, Bradshaw, Lana, Hoy, Julia, Murray, Peter and Kopp, Steven. 2021. "Clinical pathology of captive endangered mahogany gliders (Petaurus gracilis) in responses to environmental change." Journal of Zoo and Wildlife Medicine. 52 (1), pp. 268-275. https://doi.org/10.1638/2019-0163
The 'Toolbox' of strategies for managing Haemonchus contortus in goats: What's in and what's out
Kearney, P. E., Murray, P. J., Hoy, J. M., Hohenhaus, M. and Kotze, A.. 2016. "The 'Toolbox' of strategies for managing Haemonchus contortus in goats: What's in and what's out." Veterinary Parasitology. 220, pp. 93-107. https://doi.org/10.1016/j.vetpar.2016.02.028
Client perspectives on desirable attributes and skills of veterinary technologists in Australia: considerations for curriculum design
Clarke, Patricia M., Al-Alawneh, John, Pitt, Rachael E., Schull, Daniel N. and Coleman, Glen T.. 2015. "Client perspectives on desirable attributes and skills of veterinary technologists in Australia: considerations for curriculum design." Journal of Veterinary Medical Education. 42 (3), pp. 217-231. https://doi.org/10.3138/jvme.0115-001R
Susceptibility of cat fleas (Siphonaptera: Pulicidae) to Fipronil and Imidacloprid using adult and larval bioassays
Rust, M. K., Vetter, R., Denholm, I., Blagburn, B., Williamson, M. S., Kopp, S., Coleman, G., Hostetler, J., Davis, W., Mencke, N., Rees, R., Foit, S. and Tetzner, K.. 2014. "Susceptibility of cat fleas (Siphonaptera: Pulicidae) to Fipronil and Imidacloprid using adult and larval bioassays." Journal of Medical Entomology. 51 (3), pp. 638-643. https://doi.org/10.1603/ME13240
A survey of macrocyclic lactone efficacy in Australian cyathostomin populations
Beasley, A. M., Kotze, A. C., Allen, K. and Coleman, G. T.. 2017. "A survey of macrocyclic lactone efficacy in Australian cyathostomin populations." Veterinary Parasitology: Regional Studies and Reports. 8, pp. 127-132. https://doi.org/10.1016/j.vprsr.2017.03.009
Adaptation of a 96-well plate larval migration inhibition test for measuring the sensitivity of cyathostomins to macrocyclic lactone anthelmintics
Beasley, A. M., Coleman, G. T. and Kotze, A. C.. 2017. "Adaptation of a 96-well plate larval migration inhibition test for measuring the sensitivity of cyathostomins to macrocyclic lactone anthelmintics." Veterinary Parasitology. 245, pp. 55-61. https://doi.org/10.1016/j.vetpar.2017.08.010
In vitro levamisole selection pressure on larval stages of Haemonchus contortus over nine generations gives rise to drug resistance and target site gene expression changes specific to the early larval stages only
Sarai, Ranbir S., Kopp, Steven R., Knox, Malcolm R., Coleman, Glen T. and Kotze, Andrew C.. 2015. "In vitro levamisole selection pressure on larval stages of Haemonchus contortus over nine generations gives rise to drug resistance and target site gene expression changes specific to the early larval stages only." Veterinary Parasitology. 211 (1-2), pp. 45-53. https://doi.org/10.1016/j.vetpar.2015.05.002
Suspected ivermectin resistance in a south-east Queensland parascaris equorum population
Beasley, A., Coleman, G. and Kotze, A. C.. 2015. "Suspected ivermectin resistance in a south-east Queensland parascaris equorum population." Australian Veterinary Journal. 93 (9), pp. 305-307. https://doi.org/10.1111/avj.12352
Susceptibility of adult cat fleas (Siphonaptera: Pulicidae) to insecticides and status of insecticide resistance mutations at the Rdl and knockdown resistance loci
Rust, Michael K., Vetter, Richard, Denholm, Ian, Blagburn, Byron, Williamson, Martin S., Kopp, Steven, Coleman, Glen, Hostetler, Joe, Davis, Wendell, Mencke, Norbert, Rees, Robert, Foit, Sabrina, Bohm, Claudia and Tetzner, Kathrin. 2015. "Susceptibility of adult cat fleas (Siphonaptera: Pulicidae) to insecticides and status of insecticide resistance mutations at the Rdl and knockdown resistance loci." Parasitology Research. 114, pp. 7-18. https://doi.org/10.1007/s00436-015-4512-1
Use of big data in the surveillance of veterinary diseases: early detection of tick paralysis in companion animals
Guernier, Vanina, Milinovich, Gabriel J., Santos, Marcos Antonio Bezerra, Haworth, Mark, Coleman, Glen and Soares Magalhaes, Ricardo J.. 2016. "Use of big data in the surveillance of veterinary diseases: early detection of tick paralysis in companion animals." Parasites and Vectors. 9 (1). https://doi.org/10.1186/s13071-016-1590-6
Preventive health care of Pony Club horses in rural New South Wales, Australia
Buckley, P., Buckley, D., Coleman, G. T. and Morton, J. M.. 2016. "Preventive health care of Pony Club horses in rural New South Wales, Australia." Australian Veterinary Journal. 94 (8), pp. 265-270. https://doi.org/10.1111/avj.12464
Temporal variation in physiological biomarkers in black flying-foxes (Pteropus alecto), Australia
McMichael, Lee, Edson, Daniel, Mayer, David, McLaughlin, Amanda, Goldspink, Lauren, Vidgen, Miranda E., Kopp, Steven, Meers, Joanne and Field, Hume. 2016. "Temporal variation in physiological biomarkers in black flying-foxes (Pteropus alecto), Australia." Ecohealth. 13 (1), pp. 49-59. https://doi.org/10.1007/s10393-016-1113-0