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Analysis of P-gp genes relative expression associated to ivermectin resistance in Haemonchus contortus larval stages from in vitro cultures (L3 and xL3) and from gerbils (Meriones unguiculatus) (L4) as models of study

Published online by Cambridge University Press:  15 February 2024

D.E. Reyes-Guerrero Open the ORCID record for D.E. Reyes-Guerrero [Opens in a new window] ,
R.I. Higuera-Piedrahita Open the ORCID record for R.I. Higuera-Piedrahita [Opens in a new window] ,
J. Maza-Lopez Open the ORCID record for J. Maza-Lopez [Opens in a new window] ,
P. Mendoza-de-Gives Open the ORCID record for P. Mendoza-de-Gives [Opens in a new window] ,
R. Camas-Pereyra Open the ORCID record for R. Camas-Pereyra [Opens in a new window]  and
M.E. López-Arellano Open the ORCID record for M.E. López-Arellano [Opens in a new window]
D.E. Reyes-Guerrero
Affiliation:
Centro Nacional de Investigación Disciplinaria en Salud Animal e Inocuidad, Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias, Carr. Fed. Cuernavaca-Cuautla 8534, C.P. 62574 Jiutepec, Mor., México Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, C.P. 04510, México
R.I. Higuera-Piedrahita
Affiliation:
Facultad de Estudios Superiores Cuautitlán, Universidad Nacional Autónoma de México, Cuautitlán-Teoloyucan Km 2.5, Col. San Sebastián Xhala. Cuautitlán, Estado de México, México
J. Maza-Lopez
Affiliation:
Centro Nacional de Investigación Disciplinaria en Salud Animal e Inocuidad, Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias, Carr. Fed. Cuernavaca-Cuautla 8534, C.P. 62574 Jiutepec, Mor., México Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad Universitaria, Ciudad de México, C.P. 04510, México
P. Mendoza-de-Gives
Affiliation:
Centro Nacional de Investigación Disciplinaria en Salud Animal e Inocuidad, Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias, Carr. Fed. Cuernavaca-Cuautla 8534, C.P. 62574 Jiutepec, Mor., México
R. Camas-Pereyra
Affiliation:
Centro Nacional de Investigación Disciplinaria en Salud Animal e Inocuidad, Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias, Carr. Fed. Cuernavaca-Cuautla 8534, C.P. 62574 Jiutepec, Mor., México
M.E. López-Arellano*
Affiliation:
Centro Nacional de Investigación Disciplinaria en Salud Animal e Inocuidad, Instituto Nacional de Investigaciones Forestales, Agrícolas y Pecuarias, Carr. Fed. Cuernavaca-Cuautla 8534, C.P. 62574 Jiutepec, Mor., México
*
Corresponding author: M.E. López-Arellano; Email: lopez.mariaeugenia@inifap.gob.mx
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Abstract

The aim of the study was to compare the relative gene expression of Haemonchus contortus P-glycoprotein genes (Hco-pgp) between fourth (L4), infective (L3), and transitory infective (xL3) larval stages as laboratory models to study ivermectin (IVM) resistance. The H. contortus resistant to IVM (IVMr) and susceptible to IVM (IVMs) strains were used to develop xL3 in vitro culture and to infect Meriones unguiculatus (gerbils) to collect L4 stages. Morphometric differences were evaluated from 25 individuals of H. contortus from each strain. Relative gene expression from xL3 and L4 was determined between comparison of IVMr stages and from IVMr vs IVMs stages. Seven Hco-pgp genes (1, 2, 3, 4, 9, 10, and 16) were analysed by RT-qPCR using L3 stage as control group, per strain, and GAPDH and β-tubulin as constitutive genes. Morphological changes were confirmed between xL3 and L4 developing oral shape, oesophagus, and intestinal tube. In addition, the body length and width showed statistical differences (p < 0.05). The Hco-pgp1, 2, 3, and 4 genes (p < 0.05) were upregulated from 7.1- to 463.82-fold changes between IVMr stages, and Hco-pgp9 (13.12-fold) and Hco-pgp10 (13.56-fold) genes showed differences between L4 and xL3, respectively. The comparative study between IVMr vs IVMs strains associated to xL3 and L4 displayed significant upregulation for most of the Hco-pgp genes among 4.89–188.71 fold-change. In conclusion, these results suggest the use of H. contortus xL3 and L4 as suitable laboratory models to study IVMr associated with Hco-pgp genes to contribute to the understanding of anthelmintic resistance.

Keywords

Haemonchuslarval stagesP-glycoproteinivermectinresistance
Type
Research Paper
Information
Journal of Helminthology , Volume 98 , 2024 , e19
Copyright
© The Author(s), 2024. Published by Cambridge University Press

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