Kombarova, S.Yu., Borisova, O.Yu., Melnikov, V.G., Gubina, N.I., Loseva, L.V., Mazurova, I.K.

Polymorphism of tox and dtxR genes in circulating strains of Corynebacterium diphtheriae

Gabrichevsky Research Institute of Epidemiology and Microbiology, Moscow; Center of Hygiene and Epidemiology in Saint-Petersburg, Russia

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, mutation in position 1252 (G→C), which corresponds 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.
Zh. Mikrobiol. (Moscow), 2009, No. 1, P. 7—11