Laboratory assays reveal diverse phenotypes among microfilariae of Dirofilaria immitis isolates with known macrocyclic lactone susceptibility status

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 n...

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Bibliographic Details
Published in:PloS one 2020-08, Vol.15 (8), p.e0237150-e0237150
Main Authors: Jesudoss Chelladurai, Jeba R.J, Martin, Katy A, Chinchilla-Vargas, Krystal, Jimenez Castro, Pablo D, Kaplan, Ray M, Brewer, Matthew T
Format: Article
Language:English
Subjects:
Anthelmintic agents
Antiparasitic agents
Assaying
Biology and Life Sciences
Canine heartworm
Cell death
Cell permeability
Coronary artery disease
Dirofilaria immitis
Drug resistance
Drug screening
Efflux
Experiments
Genetic aspects
Glycoproteins
Health aspects
Heart diseases
Infectious diseases
Iodides
Laboratories
Lactones
Macrocycles
Medicine and Health Sciences
Metabolism
Methods
Microbial drug resistance
Motility
Nematodes
P-Glycoprotein
Parasites
Parasitological research
Pathology
Phenotypes
Physical Sciences
Physiological aspects
Prophylaxis
Propidium iodide
Research and analysis methods
Veterinary colleges
Veterinary medicine
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0237150