Heidari Soudabeh, Bandehpour Mojgan, Seyyed-Tabaei Seyyed-Javad, Valadkhani Zarintaj, Haghighi Ali, Abadi Alireza, Kazemi Bahram
Parasitology and Mycology Dept. Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran ; Biotechnology Dept. Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Iran J Parasitol. 2013 Jul;8(3):402-7.
Trichomonas vaginalis causes trichomoniasis and metronidazole is its chosen drug for treatment. Ferredoxin has role in electron transport and carbohydrate metabolism and the conversion of an inactive form of metronidazole (CO) to its active form (CPR). Ferredoxin gene mutations reduce gene expression and increase its resistance to metronidazole. In this study, the frequency of ferredoxin gene mutations in clinical isolates of T.vaginalis in Tehran has been studied.
Forty six clinical T. vaginalis isolates of vaginal secretions and urine sediment were collected from Tehran Province since 2011 till 2012. DNA was extracted and ferredoxin gene was amplified by PCR technique. The ferredoxin gene PCR products were sequenced to determine gene mutations.
In four isolates (8.69%) point mutation at nucleotide position -239 (the translation start codon) of the ferredoxin gene were detected in which adenosine were converted to thymine.
Mutation at nucleotide -239 ferredoxin gene reduces translational regulatory protein's binding affinity which concludes reduction of ferredoxin expression. For this reduction, decrease in activity and decrease in metronidazole drug delivery into the cells occur. Mutations in these four isolates may lead to resistance of them to metronidazole.
阴道毛滴虫可引起滴虫病,甲硝唑是其首选治疗药物。铁氧化还原蛋白在电子传递、碳水化合物代谢以及将甲硝唑的无活性形式(CO)转化为其活性形式(CPR)过程中发挥作用。铁氧化还原蛋白基因突变会降低基因表达,并增加其对甲硝唑的耐药性。在本研究中,对德黑兰阴道毛滴虫临床分离株中铁氧化还原蛋白基因突变的频率进行了研究。
2011年至2012年期间,从德黑兰省收集了46份阴道分泌物和尿沉渣的阴道毛滴虫临床分离株。提取DNA,并通过PCR技术扩增铁氧化还原蛋白基因。对铁氧化还原蛋白基因PCR产物进行测序以确定基因突变。
在4株分离株(8.69%)中,检测到铁氧化还原蛋白基因核苷酸位置-239(翻译起始密码子)处的点突变,其中腺苷被转化为胸腺嘧啶。
铁氧化还原蛋白基因核苷酸-239处的突变降低了翻译调节蛋白的结合亲和力,这导致铁氧化还原蛋白表达减少。由于这种减少,活性降低,甲硝唑进入细胞的量减少。这4株分离株中的突变可能导致它们对甲硝唑产生耐药性。