The diversity of ABC transporter genes across the Phylum Nematoda

Langeland, Andrea; Jetter, Haley; O'Halloran, Damien M.

doi:10.1016/j.parint.2021.102357

Cited by 9 publications

(4 citation statements)

References 36 publications

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“… 63 Among the ABC transporters, the xenobiotic efflux pump P-glycoprotein (PGP) plays an important part in the sensitivity of nematodes to anthelmintic drugs. 14 , 60 , 63 , 64 , 65 , 66 Inhibition of PGPs decreases the efflux of the active drug from the nematode and thus increases the concentration of the drug within the nematode. For instance, the calcium (Ca 2+ ) channel blocker verapamil has previously been reported as a PGP inhibitor able to potentiate the efficacy of the anthelmintic drug ivermectin against blood-sucking Haemonchus contortus larvae 67 and C. elegans larvae.…”

Section: Resultsmentioning

confidence: 99%

Biochemometry identifies ostruthin as pluripotent antimicrobial and anthelmintic agent from masterwort

Zwirchmayr¹,

Cruz²,

Grienke³

et al. 2023

iScience

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Section: Resultsmentioning

confidence: 99%

Biochemometry identifies ostruthin as pluripotent antimicrobial and anthelmintic agent from masterwort

Zwirchmayr¹,

Cruz²,

Grienke³

et al. 2023

iScience

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“…Since the assays tested in this study were based on metabolism and efflux, the transcription of candidate genes associated with these functions were studied ( Fig 6 ). The ABC transporter family is greatly expanded in number in a parasitic nematodes [ 42 ] compared to mammals. In D .…”

Section: Discussionmentioning

confidence: 99%

Strain-level variations of Dirofilaria immitis microfilariae in two biochemical assays

Hampton,

Smith,

Brewer

et al. 2024

PLoS ONE

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Background The increase in reports of resistance to macrocyclic lactones in the canine heartworm, Dirofilaria immitis is alarming. While DNA based tests have been well-validated, they can be expensive. In a previous study, we showed that two biochemical tests adapted to a 96- well plate format and read in a spectrophotometer could detect differences among lab validated D. immitis isolates. The two tests- Resazurin reduction and Hoechst 33342 efflux—detect metabolism and P-glycoprotein activity respectively in microfilariae isolated from infected dog blood. Methods Our objective was to optimize the two assays further by testing various assay parameters in D. immitis isolates not tested previously. We tested microfilarial seeding density, incubation time and the effect of in vitro treatment with ivermectin and doxycycline in five other D. immitis isolates—JYD-34, Big Head, Berkeley, Georgia III and LOL. All assays were performed in 3 technical replicates and 2–4 biological replicates. To understand the molecular basis of the assays, we also performed qPCR for selected drug metabolism and elimination associated genes of the ABC transporter and cytochrome P450 gene families. Results Metabolism and ABC transporter activity as detected by these assays varied between strains. Anthelmintic status (resistant or susceptible) did not correlate with metabolism or P-gp efflux. Basal transcriptional variations were found between strains in ABC transporter and cytochrome P450 genes. Conclusions These assays provide a greater understanding of the biochemical variation among isolates of D. immitis, which can be exploited in the future to develop in vitro diagnostic tests capable of differentiating susceptible and resistant isolates.

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“…WBPS15) ( Howe et al 2017 ). GluCl subunits were predicted from each genome using hidden Markov models (HMMs) as described previously ( Langeland et al 2020 , 2021 ; Wheeler et al 2020 ; Bode and O’Halloran 2021 ). The Pfam ( Finn et al 2014 ) HMM, PF02932 ( Neur_chan_memb ), was used alongside an HMM based on known GluCl proteins that was generated using hmmbuild ( Mistry et al 2013 ).…”

Section: Methodsmentioning

confidence: 99%

Database of glutamate-gated chloride (GluCl) subunits across 125 nematode species: patterns of gene accretion and sequence diversification

O'Halloran

2021

G3 Genes|Genomes|Genetics

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Glutamate Gated Chloride (GluCl) channels belong to the Cys-loop receptor superfamily. GluCl channels are activated by glutamate (Glu) and form substrates for the anti-parasitic drugs from the avermectin family. GluCl channels are pentameric, and each subunit contains an N-terminal extracellular domain that binds Glu and four helical transmembrane domains (TMs), which contain binding sites for avermectin drugs. In order to provide more insight into phylum-wide patterns of GluCl subunit gene expansion and sequence diversity across nematodes, we have developed a database of predicted GluCl subunit genes from 125 nematode species. Our analysis into this dataset described assorted patterns of species-specific GluCl gene counts across different nematodes as well as sequence diversity in key residues thought to be involved in avermectin binding.

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The diversity of ABC transporter genes across the Phylum Nematoda

Cited by 9 publications

References 36 publications

Biochemometry identifies ostruthin as pluripotent antimicrobial and anthelmintic agent from masterwort

Biochemometry identifies ostruthin as pluripotent antimicrobial and anthelmintic agent from masterwort

Strain-level variations of Dirofilaria immitis microfilariae in two biochemical assays

Database of glutamate-gated chloride (GluCl) subunits across 125 nematode species: patterns of gene accretion and sequence diversification

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