Parasitic Worm Motility and Viability

ACEA Biosciences xCELLigence

Parasitic Worm Motility and ViabilityDespite the prevalence and expense of parasitic worm (helminth) infection worldwide, the helminth-specific pharmacopeia is extremely limited.  This is historically due, in part, to the paucity of objective high-throughput drug screening methods amenable to the life cycle of these parasites.  Though hampered by observer subjectivity and low throughput capacity, for many years the gold standard assay for anthelmintic drug screening involved manual in vitro assessment of worm motility using a microscope.  However, it was recently shown that xCELLigence® real-time impedance monitoring is able to quantify parasitic worm motility (which is a surrogate of viability).

When a helminth is placed within an E-Plate® well, its movement/writhing changes the electrode surface area being contacted, and the resultant impedance changes can be used to quantify worm motility/viability (see figure).  Since this initial discovery, xCELLigence® has been adopted within this research community for looking at multiple helminth species and different developmental stages.  The ability to quantitatively monitor multiple developmental stages is particularly important as it allows a broader net to be cast during drug screening efforts: as each stage in a parasitic worm’s life cycle may display differential drugability, being able to monitor multiple stages increases the chances of success.

Application of xCELLigence® to parasitic worm studies serves to further expound upon a theme already well established in the area of cell-based assays: the sensitivity and flexibility of real-time impedance measurement using xCELLigence® enables researchers to easily and cheaply study phenomena that were previously either inaccessible or very laborious, costly, inefficient, and poorly reproducible.

Key Benefits of Using xCELLigence for Studying Worm Motility/Viability:
  • Objective quantification: Subjective human observations of worm motility are replaced with objective real-time data.
  • Reduced workload: Once worms are placed in the wells of an E-Plate® and data acquisition has been initiated, no further involvement is required. Data is continuously recorded for anywhere from minutes to days/weeks.
  • Flexibility: A wide range of buffer compositions can be used, and multiple developmental stages of the worm can be evaluated. Moreover, the frequency of the AC current used to measure impedance can be adjusted, enabling optimization of signal to noise ratio.
Worm Motility/Viability Supporting Information:

  • Worm Motility/Viability Publications:
  1. A novel high throughput assay for anthelmintic drug screening and resistance diagnosis by real-time monitoring of parasite motility. Smout MJ, Kotze AC, McCarthy JS, Loukas A.  PLoS Negl Trop Dis. 2010 Nov 16;4(11):e885.
  2. Viability of developmental stages of Schistosoma mansoni quantified with xCELLigence worm real-time motility assay (xWORM). Rinaldi G, Loukas A, Brindley PJ, Irelan JT, Smout MJ.  (2015).  Int J Parasitol Drugs Drug Resist. 2015 Aug 6;5(3):141-8.
  3. Reversible paralysis of Schistosoma mansoni by forchlorfenuron, a phenylurea cytokinin that affects septins. Zeraik AE, Galkin VE, Rinaldi G, Garratt RC, Smout MJ, Loukas A, Mann VH, Araujo AP, DeMarco R, Brindley PJ. Int J Parasitol. 2014 Jul;44(8):523-31.
  4. Transcriptional Responses of In Vivo Praziquantel Exposure in Schistosomes Identifies a Functional Role for Calcium Signaling Pathway Member CamKII. You H, McManus DP, Hu W, Smout MJ, Brindley PJ, Gobert GN.    PLoS Pathog. 2013 Mar;9(3):e1003254.
  5. Exploration of novel in vitro assays to study drugs against Trichuris spp. Silbereisen A, Tritten L, Keiser J. J Microbiol Methods. 2011 Nov;87(2):169-75.
  6. Comparison of novel and existing tools for studying drug sensitivity against the hookworm Ancylostoma ceylanicum in vitro. Tritten L, Braissant O, Keiser J.  2012 Mar;139(3):348-57.