摘要
Objective:To identify the frequencies(F) of ferredoxin and nitroreductase mutations were identified on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide can be prescribed as suitable drug for symptomatic to metronidazoleresistant giardiasis.Methods:Forty Giardia lamblia isolates as of 38 symptomatic and two metronidazole-resistant patients were collected from Iran.DNAs were extracted and amplified by targeting ferredoxin and Gl NR 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:-0.44013) were identified by analyzing ferredoxin gene in four symptomatic and two resistant isolates.Only,two haplotypes(F:5%,HD:0.345; Tajima's D:0.77815) characterized in metronidazole-resistant isolates of Gl NR,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 Gl NR demonstrates that nitazoxanide can be prescribed as promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in Iranian clinical isolates.
Objective:To identify the frequencies(F) of ferredoxin and nitroreductase mutations were identified on Iranian clinical isolates of Giardia lamblia in order to predict whether the nitazoxanide can be prescribed as suitable drug for symptomatic to metronidazoleresistant giardiasis.Methods:Forty Giardia lamblia isolates as of 38 symptomatic and two metronidazole-resistant patients were collected from Iran.DNAs were extracted and amplified by targeting ferredoxin and Gl NR 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:-0.44013) were identified by analyzing ferredoxin gene in four symptomatic and two resistant isolates.Only,two haplotypes(F:5%,HD:0.345; Tajima's D:0.77815) characterized in metronidazole-resistant isolates of Gl NR,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 Gl NR demonstrates that nitazoxanide can be prescribed as promising alternative treatment for symptomatic to metronidazole-resistant giardiasis in Iranian clinical isolates.
基金
financially supported by Immunology Research Center,Tabriz University of Medical Sciences,Tabriz,Iran
the master’s thesis of the first author(Thesis No.93/2-4/12)
