Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions

Kotze, Andrew C.; Hunt, Peter W.; Skuce, Philip; Samson‐Himmelstjerna, Georg von; Martin, R. J.; Sager, Heinz; Krücken, Jürgen; Hodgkinson, Jane E.; Lespine, Anne; Jex, Aaron R.; Gilleard, John S.; Beech, Robin N.; Wolstenholme, Adrian J.; Demeler, Janina; Robertson, Alan P.; Charvet, Claude; Neveu, Cédric; Kaminsky, Ronald; Rufener, Lucien; Alberich, Mélanie; Ménez, Cécile; Prichard, Roger K.

doi:10.1016/j.ijpddr.2014.07.007

Cited by 170 publications

(193 citation statements)

References 188 publications

(235 reference statements)

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“…Recently, Kotze et al [20] referred to a similar unpublished finding by Skuce et al presented at the 2013 Consortium for Anthelmintic Resistance and Susceptibility (CARS) Symposium, which supports our findings reported here. The T687G SNP therefore cannot be a universal molecular marker for TCBZ resistance.…”

Section: Tablesupporting

confidence: 92%

The T687G SNP in a P-glycoprotein gene of Fasciola hepatica is not associated with resistance to triclabendazole in two resistant Australian populations

Elliott

Spithill

2014

Molecular and Biochemical Parasitology

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Section: Tablesupporting

confidence: 92%

The T687G SNP in a P-glycoprotein gene of Fasciola hepatica is not associated with resistance to triclabendazole in two resistant Australian populations

Elliott

Spithill

2014

Molecular and Biochemical Parasitology

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“…As a consequence of their excessive use, resistance against BZ has developed and spread in H. contortus and related strongylid nematodes (Waller, 1997, Jackson and Coop, 2000, Kaplan, 2004). β-tubulin is the target for BZs (Kohler, 2001, Kotze et al., 2014), and, collectively, studies to date recognise three different single nucleotide polymorphisms (SNPs) in the isotype-1 β-tubulin gene at codons 167 (T T C to T A C; F167Y) (Silvestre and Cabaret, 2002), 198 (G A A to G C A; E198A) (Ghisi et al., 2007, Rufener et al., 2009) and 200 (T T C to T A C; F200Y) (Kwa et al., 1994, Kwa et al., 1995) to be associated with BZ resistance in H. contortus. F200Y has been detected at high prevalence in many countries and appears to be the commonest SNP linked to BZ resistance (Kotze et al., 2014).…”

Section: Introductionmentioning

confidence: 99%

Two benzimidazole resistance-associated SNPs in the isotype-1 β-tubulin gene predominate in Haemonchus contortus populations from eight regions in China

Zhang

Gasser

Yang

et al. 2016

International Journal for Parasitology: Drugs and Drug Resistan

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Haemonchus contortus is one of the most important parasitic nematodes of small ruminants around the world, particularly in tropical and subtropical regions. The control of haemonchosis relies mainly on anthelmintics, but the excessive and prolonged use of anthelmintics is causing serious drug resistance issues in many countries. As benzimidazole (BZ) anthelmintics have been broadly used in China, we hypothesized that resistance is widespread. Given the link between three known single nucleotide polymorphisms (SNPs, designated F167Y, E198A and F200Y) in the isotype-1 β-tubulin gene and BZ resistance, our goal here was to explore the presence of these mutations in H. contortus from small ruminants (sheep and goats) from eight provinces in China using PCR-coupled sequencing. In addition, the genetic diversity and genetic relationship of isotype-1 β-tubulin sequence haplotypes were also investigated. Among 192 H. contortus adult individuals representing the eight populations, we identified six distinct sequence types, five of which had SNP E198A (GCA) and/or F200Y (TAC). Sequence analysis showed that the frequencies of SNPs E198A and F200Y were 0–70% and 0–31%, respectively. SNP F167Y (TAC) was not detected in any population. In addition, high haplotype diversities (0.455–0.939) and nucleotide diversities (0.018–0.039) were calculated. A network analysis of the isotype-1 β-tubulin gene sequences showed that SNPs E198A and F200Y occurred in multiple distinct groupings, suggesting multiple independent origins of these SNPs. The findings of this first study of SNPs in the isotype-1 β-tubulin gene of H. contortus populations suggest that BZ resistance is prevalent in some regions of China, and that any control strategy might focus on monitoring BZ resistance in this country.

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“…Next-generation sequencing (NGS) technologies have enabled the high-throughput and genome-scale screening of eukaryotic pathogens, and have been useful in identifying drug targets and elucidating drug resistance mechanisms (4,5). The development of RNA interference (RNAi) target sequencing (RIT-Seq) in kinetoplastid parasites, such as Trypanosoma brucei (6), has revealed numerous genes associated with drug action (7); however, RNAibased screening is not applicable to Leishmania, because most species lack functional RNAi machinery (8).…”

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confidence: 99%

Cos-Seq for high-throughput identification of drug target and resistance mechanisms in the protozoan parasite Leishmania

Gazanion

Fernández-Prada

Papadopoulou

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

106

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Innovative strategies are needed to accelerate the identification of antimicrobial drug targets and resistance mechanisms. Here we develop a sensitive method, which we term Cosmid Sequencing (or "Cos-Seq"), based on functional cloning coupled to next-generation sequencing. Cos-Seq identified >60 loci in the Leishmania genome that were enriched via drug selection with methotrexate and five major antileishmanials (antimony, miltefosine, paromomycin, amphotericin B, and pentamidine). Functional validation highlighted both known and previously unidentified drug targets and resistance genes, including novel roles for phosphatases in resistance to methotrexate and antimony, for ergosterol and phospholipid metabolism genes in resistance to miltefosine, and for hypothetical proteins in resistance to paromomycin, amphothericin B, and pentamidine. Several genes/loci were also found to confer resistance to two or more antileishmanials. This screening method will expedite the discovery of drug targets and resistance mechanisms and is easily adaptable to other microorganisms.

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Recent advances in candidate-gene and whole-genome approaches to the discovery of anthelmintic resistance markers and the description of drug/receptor interactions

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Cited by 170 publications

References 188 publications

The T687G SNP in a P-glycoprotein gene of Fasciola hepatica is not associated with resistance to triclabendazole in two resistant Australian populations

The T687G SNP in a P-glycoprotein gene of Fasciola hepatica is not associated with resistance to triclabendazole in two resistant Australian populations

Two benzimidazole resistance-associated SNPs in the isotype-1 β-tubulin gene predominate in Haemonchus contortus populations from eight regions in China

Cos-Seq for high-throughput identification of drug target and resistance mechanisms in the protozoan parasite Leishmania

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