title: Development of metronidazole-resistant lines of Blastocystis sp.
abstract: Metronidazole (MTR) is frequently used for the treatment of Blastocystis infections, but with variable effectiveness, and often with treatment failures as a possible result of drug resistance. We have developed two Blastocystis MTR-resistant (MTR(R)) subtype 4 WR1 lines (WR1-M4 and WR1-M5), with variable susceptibility to a panel of anti-protozoal agents including various 5-nitroimidazoles, nitazoxanide and furazolidone. WR1-M4 and WR1-M5 were developed and assessed over an 18-month period and displayed persistent MTR resistance, being more than 2.5-fold less susceptible to MTR than the parent isolate. The MTR(R) lines grew with a similar g time to WR1, but were morphologically less consistent with a mixture of size. All Blastocystis isolates and the MTR(R) lines were most susceptible to the 5-nitroimidazole drug ronidazole. WR1-M5 was apparently cross-resistant to satranidazole and furazolidone, and WR1-M4 was cross-resistant to nitazoxanide. These MTR(R) lines now provide a valuable tool for the continued assessment of the efficacy and mechanism of action of new and established drugs against a range of Blastocystis sp. subtypes, in order to identify a universally effective drug and to facilitate understanding of the mechanisms of drug action and resistance in Blastocystis.
authors.affiliation: Queensland Institute of Medical Research, PO Royal Brisbane Hospital, 4029, Herston, Queensland, Australia. Linda.Dunn@qimr.edu.au
authors.forename: L A
authors.initials: LA
authors.lastname: Dunn
authors.forename: K S W
authors.initials: KS
authors.lastname: Tan
authors.forename: P
authors.initials: P
authors.lastname: Vanelle
authors.forename: T
authors.initials: T
authors.lastname: Juspin
authors.forename: M D
authors.initials: MD
authors.lastname: Crozet
authors.forename: T
authors.initials: T
authors.lastname: Terme
authors.forename: P
authors.initials: P
authors.lastname: Upcroft
authors.forename: J A
authors.initials: JA
authors.lastname: Upcroft
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D016844:Blastocystis / Q000187:drug effects*; D004351:Drug Resistance; D008795:Metronidazole / Q000494:pharmacology*
chemical_list: D000981:Antiprotozoal Agents; D008795:Metronidazole