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

dc.contributor.author Jesudoss Chelladurai, Jeba
dc.contributor.author Brewer, Matt
dc.contributor.author Martin, Katy
dc.contributor.author Chinchilla-Vargas, Krystal
dc.contributor.author Jimenez Castro, Pablo
dc.contributor.author Kaplan, Ray
dc.contributor.author Brewer, Matthew
dc.contributor.department Veterinary Pathology
dc.date 2020-08-13T20:04:45.000
dc.date.accessioned 2021-02-26T13:48:36Z
dc.date.available 2021-02-26T13:48:36Z
dc.date.copyright Wed Jan 01 00:00:00 UTC 2020
dc.date.issued 2020-08-06
dc.description.abstract <p>Prevention of canine heartworm disease caused by <em>Dirofilaria immitis</em> relies on chemoprophylaxis with macrocyclic lactone anthelmintics. Alarmingly, there are increased reports of <em>D</em>. <em>immitis</em> 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 <em>D</em>. <em>immitis</em> 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 <em>D</em>. <em>immitis</em> microfilariae, and caution should be applied when adapting cell death assays to drug screening studies for nematode parasites.</p>
dc.description.comments <p>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." <em>PLoS ONE</em> 15, no. 8 (2020): e0237150. DOI: <a href="https://doi.org/10.1371/journal.pone.0237150" target="_blank">10.1371/journal.pone.0237150</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/vpath_pubs/110/
dc.identifier.articleid 1113
dc.identifier.contextkey 18906514
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath vpath_pubs/110
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/98915
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/vpath_pubs/110/2020_BrewerMatthew_LaboratoryAssays.pdf|||Fri Jan 14 18:40:17 UTC 2022
dc.source.uri 10.1371/journal.pone.0237150
dc.subject.disciplines Small or Companion Animal Medicine
dc.subject.disciplines Veterinary Pathology and Pathobiology
dc.title Laboratory assays reveal diverse phenotypes among microfilariae of Dirofilaria immitis isolates with known macrocyclic lactone susceptibility status
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 5da9e3cf-a247-450d-98e7-74c92c5ea8a9
relation.isOrgUnitOfPublication cf38d7e3-b5f8-4859-83e3-ae8fab6a4c5f
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