Campus Units

Veterinary Pathology

Document Type

Article

Publication Version

Published Version

Publication Date

8-6-2020

Journal or Book Title

PLoS ONE

Volume

15

Issue

8

First Page

e0237150.

DOI

10.1371/journal.pone.0237150

Abstract

Prevention of canine heartworm disease caused by Dirofilaria immitis relies on chemoprophylaxis with macrocyclic lactone anthelmintics. Alarmingly, there are increased reports of D. immitis isolates with resistance to macrocyclic lactones and the ability to break through prophylaxis. Yet, there is not a well-established laboratory assay that can utilize biochemical phenotypes of microfilariae to predict drug resistance status. In this study we evaluated laboratory assays measuring cell permeability, metabolism, and P-glycoprotein-mediated efflux. Our assays revealed that trypan blue, propidium iodide staining, and resazurin metabolism could detect differences among D. immitis isolates but none of these approaches could accurately predict drug susceptibility status for all resistant isolates tested. P-glycoprotein assays suggested that the repertoire of P-gp expression is likely to vary among isolates, and investigation of pharmacological differences among different P-gp genes is warranted. Further research is needed to investigate and optimize laboratory assays for D. immitis microfilariae, and caution should be applied when adapting cell death assays to drug screening studies for nematode parasites.

Comments

This article is published as Jesudoss Chelladurai, Jeba RJ, Katy A. Martin, Krystal Chinchilla-Vargas, Pablo D. Jimenez Castro, Ray M. Kaplan, and Matthew T. Brewer. "Laboratory assays reveal diverse phenotypes among microfilariae of Dirofilaria immitis isolates with known macrocyclic lactone susceptibility status." PLoS ONE 15, no. 8 (2020): e0237150. DOI: 10.1371/journal.pone.0237150. Posted with permission.

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

Copyright Owner

Jesudoss Chelladurai et al.

Language

en

File Format

application/pdf

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