Email this article POLYMORPHISM OF tox AND dtxR GENES IN CIRCULATING STRAINS OF CORYNEBACTERIUM DIPHTHERIAE
- Authors: Kombarova S.Y.1,2, Borisova O.Y.1,2, Melnikov V.G1,2, Gubina N.I1,2, Loseva L.V1,2, Mazurova I.K1,2
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Affiliations:
- Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow
- Center of Hygiene and Epidemiology in Saint-Petersburg, Russia
- Issue: Vol 86, No 1 (2009)
- Pages: 7-11
- Section: Articles
- Submitted: 09.06.2023
- Published: 15.02.2009
- URL: https://microbiol.crie.ru/jour/article/view/13230
- ID: 13230
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Abstract
Polymorphism of tox and dtxR genes responsible for diphtheria toxin synthesis was revealed. Seven point mutations in tox gene were detected; study of their combinations allowed to determine 10 allelic variants of the tox gene in C.diphtheriae strains. Majority of mutations did not lead to changes in substitutions in amino acid sequence of diphtheria toxin. In tox gene from 2 strains of mitis biovar, ribotype «Otchakov» isolated in Saint-Petersburg, mutatio n in position 1252 (G → C) , which corre- sponds to change of glycine on arginine in amino acid sequence of diphtheria toxin (G393R), was identified. Mutation localizes in R domain of fragment B of diphtheria toxin. In the dtxR gene 16 point mutations were registered; study of their combinations allowed to determine 10 allelic variants of the dtxR gene. Two mutations led to amino acid substitutions in regulatory protein DtxR: in position 640 (C→A), which corresponds to change of leucine on isoleucine (L214I), and in position 440 (C→T), which corresponds to change of alanine on valine (A147V). Mutation A147V is characteristic for all strains of epidemic clonal group (strains of biovar gravis , ribotype «Sankt-Peterburg/Rossija», enzymetypes of complex 8), dominated in Russia during diphtheria epidemic at 1990s. Strains of this group were characterized by high level of diphtheria toxin production.
Full Text
ПОЛИМОРФИЗМ ГЕНОВ tox И dtxR У ЦИРКУЛИРУЮЩИХ ШТАММОВ CORYNEBACTERIUM DIPHTHERIAE×
About the authors
S. Yu Kombarova
Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow; Center of Hygiene and Epidemiology in Saint-Petersburg, Russia
O. Yu Borisova
Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow; Center of Hygiene and Epidemiology in Saint-Petersburg, Russia
V. G Melnikov
Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow; Center of Hygiene and Epidemiology in Saint-Petersburg, Russia
N. I Gubina
Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow; Center of Hygiene and Epidemiology in Saint-Petersburg, Russia
L. V Loseva
Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow; Center of Hygiene and Epidemiology in Saint-Petersburg, Russia
I. K Mazurova
Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow; Center of Hygiene and Epidemiology in Saint-Petersburg, Russia
References
- Алтухов Ю.П. Генетические процессы в популяциях. М., Академкнига, 2003.
- Борисова О.Ю. Патогенные и молекулярногенетические свойства штаммов С.diphtheriae, циркулирующих на территории России в течение 1994 - 1998 гг. Автореф. дис. канд. мед. наук. М., 1999.
- Колодкина В.Л., Титов Л.П., Шарапа Т.Н. и др. Сайты точечных мутаций промоторной области tox-гена и гена регулятора dtxR, ассоциированные с уровнем токсинопродукции Corynebacterium diphtheriae, изолированных в Беларуси. Мол. ген. микробиол. вирусол. 2007, 1: 22 - 29.
- Комбарова С.Ю., Мазурова И.К., Мельников В.Г. и др. Генетическая структура штаммов Corynebacterium diphtheriae, выделенных в России при разной интенсивности эпидемического процесса дифтерии. Журн. микробиол. 2001, 3: 3 - 8.
- Комбарова С.Ю. Микробиологический и молекулярно-генетический мониторинг возбудителя дифтерийной инфекции. Автореф. дис. д-ра биол. наук. М., 2007.
- Костюкова Н.Н. Уроки дифтерии. Журн. микробиол. 1999, 2: 92 - 96.
- Корженкова М.П. Клиника дифтерии в период высокой и низкой заболеваемости. Вакцинация. Новости вакцинопроф. 2006, 1 (43): 4 - 6.
- Мазурова И.К. Комплексная система лабораторной диагностики и наблюдения за возбудителем дифтерии. Автореф. дис. д-ра мед. наук. М., 1993.
- Мазурова И.К., Мельников В.Г., Комбарова С.Ю. и др. Лабораторная диагностика дифтерийной инфекции. Метод. указ. МУК 4.2.698-98. М., 1998.
- Маркина С.С., Максимова Н.М., Черкасова В.В. и др. Эпидемиологическая ситуация по дифтерии в настоящее время. Вакцинация. Новости вакцинопроф. 2006, 1 (43): 7 - 11.
- Cerdeno-Tarraga A.M., Dover L.G., Holden M.T.G. et al. The complete genome sequence and analysis of Corynebacterium diphtheriae NCTC 12129. Nucl. Acids Res. 2003, 31 (22): 6516 - 6523.
- Grimont P.A.D., Grimont F., Efstratiou A. et.al. International nomenclature for Corynebacterium diphtheriae ribotypes. Res. Microbiol. 2004, 155 (3): 162 - 166.
- Holmes R. Biology and molecular biology of diphtheria toxin and tox gene. J. Infect. Dis. 2000, 5 (6): 156 - 167.
- Love J.F., Van der Spek J.R., Marin V. et al. Genetic and biophysical studies of diphtheria toxin repressor (DtxR) and the hyperactive mutant DtxR (E175K) support a multistep model activation. Proc. Natl. Acad. Sci. USA. 2004, 101 (8): 2506 - 2511.
- Nakao H., Pruckler J.M., Mazurova I.K. et. al. Heterogeneity of diphtheria toxin gene, tox, and its regulatory element, dtxR, in Corynebacterim diphtheriae strains causing epidemic diphtheria in Russia and Ukraine. J. Clin. Microbiol. 1996, 34 (7): 1711 - 17.
- Popovic T., Kombarova S., Reeves M.W. et.al. Molecular epidemiology of diphtheria in Russia, 1985 - 1994. J. Infect. Dis. 1996, 174: 1064 - 1072.
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