چکیده (انگلیسی):

Objective: To identify the frequencies (F) of ferredoxin and nitroreductase mutations
on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide
can be prescribed as suitable drug for symptomatic to metronidazole-resistant
giardiasis.
Methods: Forty Giardia lamblia isolates as of 38 symptomatic and two metronidazoleresistant
patients were collected from Iran. DNAs were extracted and amplified by targeting
ferredoxin and GlNR genes. The amplicons were directly sequenced to determine
gene mutations.
Results: The various amino acid substitutions (F: 20%, Haplotype diversity: 0.891,
Tajima's D: −0.440 13) were identified by analyzing ferredoxin gene in four symptomatic
and two resistant isolates. Only two haplotypes (F: 5%, HD: 0.345; Tajima's D: 0.778 15)
characterized in metronidazole-resistant isolates of GlNR, however, no point mutations
was found in symptomatic isolates.
Conclusions: Non-synonymous mutations of ferredoxin oxidoreductase gene reduce
translational regulatory protein's binding affinity which concludes reduction of ferredoxin
expression and its activity. This leads to decrease in metronidazole drug delivery into the
cells. Mutations in these isolates may lead to their resistance to metronidazole. No to low
synonymous mutations of GlNR demonstrates that nitazoxanide can be prescribed as
promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in
Iranian clinical isolates.