Selection and characterization of Toxoplasma gondii mutants resistant to artemisinin

Randolph L. Berens, Edward C. Krug, Paul B. Nash, Tyler J. Curiel

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Toxoplasma gondii infection, like malaria, is sensitive to inhibition by artemisinin (ART). Mechanisms of action for ART in malaria treatment have been proposed, but little is known about its effects in T. gondii infection. To better understand its inhibitory effects on T. gondii, mutants resistant to ART were selected by progressive culture in permissive levels of the drug. Five clonal isolates were established and characterized. The isolates were ~65-fold less sensitive to ART than is the parental RH and showed cross- resistance to the ART derivatives dihydroartemisinin and artemether. In addition to ART resistance, 1 clone (C9) formed morphologically unusual parasitophorous vacuoles and another (A2) was avirulent for mice and protected mice from challenge with the wild type. These clonal T. gondii mutant isolates will be useful for the study of not only the mechanism of action of ART but also parasite vacuole biology and virulence factors.

Original languageEnglish (US)
Pages (from-to)1128-1131
Number of pages4
JournalJournal of Infectious Diseases
Volume177
Issue number4
DOIs
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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