Ferredoxin Gene Mutation in Iranian Trichomonas vaginalis Isolates.
AbstractBackground: 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. Methods: 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. Results: 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. Conclusion: 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.
Wolner-Hanssen P, Krieger JN, Stevens CE, Kiviat NB, Koutsky L, Critchlow C, et al. Clinical manifestations of vaginal trichomo-niasis. JAMA. 1989;261:571-6.
Minkoff H, Grunebaum AN, Schwarz RH, Feldman J, Cummings M, Crombleholme W, et al. Risk factors for prematurity and pre-mature rupture of membranes: a prospective study of the vaginal flora in pregnancy. Am J Obstet Gynecol. 1984;150:965-72.
Markarian DS, Popova EA, Arshba AM, Sulukhiia RV, Cherkezila GK. Cases of Down’s syndrome in children of young parents with choronic inflammatory genital diseases and secondary disorders of spermatogenesis. Akusb Ginekol (Mosk). 1990;5:38-41. [Article in Russian]
Hoffman DS, Brown GD, Wirth FH, Gebert BS, Bailey CL, Anday EK. Urinary tract infection with Trichomonas vaginalis in a pre-mature newborn infant and the development of chronic lung disease. J Perinatol. 2003;23:59.
Super DE, Bumpt RC, Hurt WG. Bacterial vaginosis and trichomoniasis vaginitis are risk factor for colitis after abdominal hysterectomy. Am J Obstet Gynecol. 1990;163(3):1016-23.
Holmes KK, Handsfield HH, Wang SP, Wentworth BB, Turck M, Anderson JB, et al. Etiology of nongonococcal urethritis. N Engl J Med. 1975;292:1199-205.
Mardh PA, Colleen S. Search for uro-genital tract infections in patients with symptoms of prostatitis. Studies on aerobic and strictly anae-robic bacteria, mycoplasmas, fungi, tricho-monads and viruses. Scand J Urol Nephrol. 1975;9:8-16.
Han Q, Liu J, Wang T, Xiao H, Fang Z. Influence of the metabolite produced by Trichomonas vaginalis on human sperm motility in vitro. Zhonghua Nan Ke Xue. 2004;10(4):272-4. [Article in Chinese]
Nicoletti N. The problem of trichomoniasis of the lower genital tract in the female. Br J Vener Dis. 1961;37:223-8.
Zhang ZF, Graham S, Yu SZ, Marshall J, Zie-lezny M, Chen YX, et al. Trichomonas vaginalis and cervical cancer. A prospective study in China. Ann Epidemiol. 1995;5:325-32.
Cosar C, Julou L. Activity of 1-(2-hydrox-yethyl)-2-methyl-5- nitroimidazole (R.P. 8823) against experimental Trichomonas vaginalis infection. Ann Inst Pasteur. 1959;96:238-41.[Article in French]
Edwards DI. Nitroimidazole drugs-action and resistance mechanisms. I. Mechanisms of action. J Antimicrob Chemother. 1993;31:9-20
Chapman A, Cammack R, Linstead D, Lloyd D. The generation of metronidazole radicals in hydrogenosomes isolated from Trichomonas vaginalis. J Gen Microbiol. 1985;131:2141-4.
Robinson SC. Trichomonal vaginitis resistant to metronidazole. Can Med Assoc J. 1962;-86:665.
Lossick JG. Therapy of urogenital trichomo-niasis,. In Honigberg B M(ed.), Trichomonads parasitic in man. Springer Verlag, New York -;1989. p. 324-341.
Sobel JD, Nagappan V, Nyirjesy P. Metroni-dazole-resistant vaginal trichomoniasis -an em-erging problem. N Engl J Med. 1999;-341(4):292-3.
Upcroft P, Upcroft JA. Drug targets and mechanisms of resistance in the anaerobic protozoa. Clin Microbiol Rev. 2001;14(1):150.
Schwebke JR, Barrientes FJ. Prevalence of Trichomonas vaginalis isolates with resistance to metronidazole and tinidazole. Antimicrob Agents Chemother. 2006;50(12):4209-10.
Land KM, Clemens DL, Johnson PJ. Loss of multiple hydrogenosomal proteins associated with organelle metabolism and high-level drug resistance in trichomonads. Exp Parasitol. 2001;97(2):102-10.
Rasoloson D, Vanacova S, Tomkova E, Razga J, Hrdy I, Tachezy J, et al. Mechanisms of in vitro development of resistance to metro-nidazole in Trichomonas vaginalis. Microbiology. 2002;148:2467-77.
Diamond LS, Harlow DR, Cunnick CC. A new medium for the axenic culture of Entamoeba histolytica and other Entamoeba. Trans R Soc Trop Med Hyg. 1978;72(4):431-2.
Quon DV, d’Oliveira CE, Johnson PJ. Reduced transcription of the ferredoxin gene in metronidazole - resistant Trichomonas vaginalis. Proc Natl Acad Sci USA. 1992;89:4402- 6.
Vidakovic M, Crossnoe CR, Neidre C, Kim K, Krause KL, Germanas JP. Reactivity of reduced [2Fe-2S[ ferredoxins parallels host susceptibility to nitroimidazoles. Antimicrob Agents Chemother. 2003;47:302- 8.
Land KM, Delgadillo-Correa MG, Tachezy J, Vanacova S, Hseih CL, Sutak R, et al. Targeted gene replacement of a ferredoxin gene in Trichomonas vaginalis does not lead to metronidazole resistance. Mol Microbiol. 2004;51:115-22.