Development of metronidazole-resistant lines of Blastocystis sp.

L A Dunn, K S W Tan, P Vanelle, T Juspin, M D Crozet, T Terme, P Upcroft, J A Upcroft

Parasitology research 2012 Jul

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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.

Citation

L A Dunn, K S W Tan, P Vanelle, T Juspin, M D Crozet, T Terme, P Upcroft, J A Upcroft. Development of metronidazole-resistant lines of Blastocystis sp. Parasitology research. 2012 Jul;111(1):441-50