A novel high throughput assay for anthelmintic drug screening and resistance diagnosis by real-time monitoring of parasite motility

Smout, Michael J., Kotze, Andrew C., McCarthy, James S. and Loukas, Alex (2010) A novel high throughput assay for anthelmintic drug screening and resistance diagnosis by real-time monitoring of parasite motility. PLoS Neglected Tropical Diseases, 4 11: e885-1-e885-10. doi:10.1371/journal.pntd.0000885

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Author Smout, Michael J.
Kotze, Andrew C.
McCarthy, James S.
Loukas, Alex
Title A novel high throughput assay for anthelmintic drug screening and resistance diagnosis by real-time monitoring of parasite motility
Journal name PLoS Neglected Tropical Diseases   Check publisher's open access policy
ISSN 1935-2735
Publication date 2010-11-01
Sub-type Article (original research)
DOI 10.1371/journal.pntd.0000885
Open Access Status DOI
Volume 4
Issue 11
Start page e885-1
End page e885-10
Total pages 10
Editor Jennifer Keiser
Place of publication San Francisco, United States
Publisher Public Library of Science
Language eng
Formatted abstract
Background: Helminth parasites cause untold morbidity and mortality to billions of people and livestock. Anthelmintic drugs are available but resistance is a problem in livestock parasites, and is a looming threat for human helminths. Testing the efficacy of available anthelmintic drugs and development of new drugs is hindered by the lack of objective highthroughput screening methods. Currently, drug effect is assessed by observing motility or development of parasites using laborious, subjective, low-throughput methods.

Methodology/Principal Findings:
Here we describe a novel application for a real-time cell monitoring device (xCELLigence) that can simply and objectively assess anthelmintic effects by measuring parasite motility in real time in a fully automated high-throughput fashion. We quantitatively assessed motility and determined real time IC50 values of different anthelmintic drugs against several developmental stages of major helminth pathogens of humans and livestock, including larval Haemonchus contortus and Strongyloides ratti, and adult hookworms and blood flukes. The assay enabled quantification of the onset of egg hatching in real time, and the impact of drugs on hatch rate, as well as discriminating between the effects of drugs on motility of drug-susceptible and -resistant isolates of H. contortus.

Conclusions/Significance:
Our findings indicate that this technique will be suitable for discovery and development of new anthelmintic drugs as well as for detection of phenotypic resistance to existing drugs for the majority of helminths and other pathogens where motility is a measure of pathogen viability. The method is also amenable to use for other purposes where motility is assessed, such as gene silencing or antibody-mediated killing.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article number e885

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Medicine Publications
 
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Created: Wed, 23 Feb 2011, 20:31:43 EST by Amarjeet Sanghera on behalf of Medicine - Royal Brisbane and Women's Hospital