Related Experiment Video

Updated: Jul 5, 2026

QTL Mapping and CRISPR/Cas9 Editing to Identify a Drug Resistance Gene in Toxoplasma gondii
11:37

QTL Mapping and CRISPR/Cas9 Editing to Identify a Drug Resistance Gene in Toxoplasma gondii

Published on: June 22, 2017

Forward genetics reveals microsporidian drug targets and recombination-based resistance

Qingyuan Huang1,2, Xianzhi Meng1,2, Winnie Zhao1

  • 1Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada.

Npj Antimicrobials and Resistance
|July 3, 2026
PubMed

Insights

Researchers identified drug targets in microsporidia, which are fungal parasites. Drug resistance evolves through new mutations in genes like beta-tubulin and topoisomerase II, which can become homozygous.

Area of Science:

  • Microbiology
  • Parasitology
  • Genetics

Background:

  • Microsporidia are significant intracellular fungal parasites affecting humans and animals.
  • Understanding microsporidian drug targets and resistance mechanisms is crucial but largely unknown.

Purpose of the Study:

  • To identify drug targets in microsporidia using forward genetics.
  • To elucidate the mechanisms of drug resistance evolution in microsporidian parasites.

Main Methods:

  • Serial passage of Nematocida parisii (a microsporidian) in C. elegans under increasing drug concentrations (albendazole, dexrazoxane).
  • Whole-genome sequencing and heterozygosity mapping to identify resistance-conferring mutations.
  • Analysis of mutations in beta-tubulin, alpha-tubulin, and topoisomerase II.

Main Results:

  • Albendazole resistance in N. parisii is associated with mutations in beta-tubulin (heterozygous or homozygous) and sometimes alpha-tubulin.
  • Dexrazoxane resistance is linked to heterozygous mutations in topoisomerase II, including in the inhibitor's binding site.
  • Loss of heterozygosity at the beta-tubulin locus was observed in strains with homozygous beta-tubulin variants.

Conclusions:

  • Forward genetics is a powerful tool for discovering microsporidian drug targets.
  • Drug resistance emerges from de novo heterozygous mutations that can subsequently become homozygous, likely through mitotic recombination.

More Related Videos

Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases09:13

Understanding the Development of Compensatory Pathways in a Mutant Malaria Parasite Harbouring Hypomorphic Allele of Plant-Like Kinases

Published on: November 22, 2024

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Related Concept Videos

Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Genetic Screens02:46

Genetic Screens

Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
Forward genetic screens
Forward or “classical” genetic screens involve creating random mutations in an organism’s DNA using radiation, mutagens, or insertion of additional bases, which result in visible changes...
Conservative Site-specific Recombination and Phase Variation02:53

Conservative Site-specific Recombination and Phase Variation

Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
Fungal Phylum Microsporidia01:28

Fungal Phylum Microsporidia

Microsporidia are a group of obligate intracellular fungi that were initially classified as protists but were later reclassified based on phylogenetic, molecular, and structural evidence linking them to the Chytridiomycota. These unicellular, non-motile organisms are highly specialized parasites that infect a wide range of animal hosts, including humans. They have evolved extensive genomic and metabolic reductions, making them highly dependent on their hosts for survival.Morphology and Genomic...
Exon Recombination02:32

Exon Recombination

The evolution of new genes is critical for speciation. Exon recombination, also known as exon shuffling or domain shuffling, is an important means of new gene formation. It is observed across vertebrates, invertebrates, and in some plants such as potatoes and sunflowers. During exon recombination, exons from the same or different genes recombine and produce new exon-intron combinations, which might evolve into new genes. 
Exon shuffling follows “splice frame rules.” Each exon has three reading...