Open AccessA Rapid, High-Throughput Viability Assay for Blastocystis spp. Reveals Metronidazole Resistance and Extensive Subtype-Dependent Variations in Drug Susceptibilities
Author(s) -
Haris Mirza,
Joshua D. W. Teo,
Jacqueline Upcroft,
Kevin S. W. Tan
Publication year - 2011
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.00900-10
Subject(s) - blastocystis , nitazoxanide , tinidazole , metronidazole , biology , mefloquine , drug resistance , microbiology and biotechnology , multiple drug resistance , ampicillin , chloroquine , antibiotics , virology , immunology , malaria , feces
Blastocystis is an emerging protistan parasite of controversial pathogenesis. Although metronidazole (Mz) is standard therapy forBlastocystis infections, there have been accumulating reports of treatment failure, suggesting the existence of drug-resistant isolates. Furthermore, very little is known aboutBlastocystis susceptibility to standard antimicrobials. In the present study, we established resazurin and XTT viability microassays forBlastocystis spp. belonging to subtypes 4 and 7, both of which have been suggested to represent pathogenic zoonotic subtypes. The optimized resazurin assay was used to screen a total of 19 compounds against both subtypes. Interestingly, subtype 7 parasites were resistant to Mz, a 1-position-substituted 5-nitroimidazole (5-NI), while subtype 4 parasites were sensitive. Some cross-resistance was observed to tinidazole, another 1-position 5-NI. Conversely, subtype 4 parasites were resistant to emetine, while subtype 7 parasites were sensitive. Position 2 5-NIs were effective against both subtypes, as were ornidazole, nitazoxanide, furazolidone, mefloquine, quinicrine, quinine, cotrimoxazole (trimethoprim-sulfamethoxazole), and iodoacetamide. Both subtypes were resistant to chloroquine, doxycycline, paromomycin, ampicillin, and pyrimethamine. This is the first study to report extensive variations in drug sensitivities among two clinically important subtypes. Our study highlights the need to reevaluate established treatment regimens forBlastocystis infections and offers clear new treatment options for Mz treatment failures.