Development of metronidazole-resistant lines of Blastocystis sp.
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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 (MTRR) 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 MTRR lines grew with a similar g time to WR1, but were morphologically less consistent with a mixture of size. All Blastocystis isolates and the MTRR 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 MTRR 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.
KeywordsRifaximin Tinidazole Furazolidone Nitazoxanide Ornidazole
This work was supported by the National Health and Medical Research Council of Australia and by U01 Cooperative Research agreement A175527 from the US National Institutes of Health (NIH). We wish to thank NgGeokChoo for growth of Blastocystis sp.WR1 in the Department of Microbiology, Singapore. We wish to thank Dr Rebecca Traub (School of Veterinary Science, University of Queensland, St. Lucia, Queensland, Australia) and Dr. Robyn Nagel (Toowoomba Gastroenterology Clinic, Medici Medical Centre, Toowoomba, Queensland, Australia) for subtyping the Netsky isolate. This study was facilitated by the commissioning of synthesis of C17 by NIH from Southern Research Institute USA. Lopinavir (cat # 9481) was obtained through NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID (contributor), NIH.
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