ORIGINAL RESEARCH

Polymorphism of the dtxR gene in the currently existing strains of Сorynebacterium diphtheriae

Chagina IA1, Perevarova YuS2, Perevarov VV2, Chaplin AV2, Borisova OYu1,2, Kafarskaya LI2, Afanas'ev SS1, Aleshkin VA1
About authors

1 G. N. Gabrichevsky Research Institute for Epidemiology and Microbiology, Moscow, Russia

2 Pirogov Russian National Research Medical University, Moscow, Russia

Correspondence should be addressed: Andrey Viktorovich Chaplin
ul. Ostrovityanova, d. 1, Moscow, Russia, 117997; moc.liamg@kidemoloko

About paper

Funding: this study was conducted as part of two projects: The Study of the Role of Microbial Communities in Human Oropharynx and Blood in Diphtheria, Pertussis and Other Infectious Inflammatory Diseases (Project ID А16-116021550311-2) and The Development of Molecular-Genetic Methods for Laboratory Diagnosis of Diphtheria and Pertussis (Project ID АААА-А16-116101810127-7) supported by the Sectoral Research Program of the Russian Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing (Problem-oriented Research in Epidemiological Surveillance of Infectious and Parasitic Diseases in 2016-2020).

Contribution of the authors to this work:Chagina IA — analysis of literature, data collection and interpretation, drafting of a manuscript; Perevarova YuS, Perevarov VV — analysis of literature, data analysis and interpretation, drafting of a manuscript; Chaplin AV — research planning, data analysis and interpretation, drafting of a manuscript; Borisova OYu — research planning, data collection and interpretation, drafting of a manuscript; Kafarskaya LI — data interpretation, drafting of a manuscript; Afanas’ev SS, Aleshkin VA — research planning, drafting of a manuscript. All authors participated in editing of the manuscript.

Received: 2017-02-02 Accepted: 2017-02-18 Published online: 2017-03-11
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The pathogenic mechanism used by Corynebacterium diphtheriae is attributed to the ability of the diphtheria toxin to disrupt protein synthesis in human cells. Diphtheria toxin production is regulated by the DtxR protein. The latter is involved in the iron-mediated repression of the toxin gene and coordinates activities of other genes essential for the survival of C. diphtheriae. The DtxR-encoding gene occurs in both toxigenic and non-toxigenic strains; therefore it can be used to analyze the population structure of the species. In our work we have studied 45 strains of C. diphtheriae isolated in the Russian Federation in 2010–2015. These strains were analyzed to reveal that gene dtxR is a highly conservative region of С. diphtheriae genome that can be found in all members of the studied species. The majority of the discovered polymorphisms were synonymous (16 of 18 single nucleotide polymorphisms identified). In spite of the low phylogenetic signal, the allelic variant of dtxR was associated with the strain’s phenotype (biovar, toxigenicity). The obtained data indicate the presence of aggressive negative selection aimed to maintain the existing protein sequence in the population. Based on the results, we recommend dtxR polymerase chain reaction as an additional technique for pathogen identification, which is especially relevant considering the increasing prevalence of the disease associated with non-toxigenic C. diphtheriae strains.

Keywords: diphtheria, Corynebacterium diphtheriae, dtxR, multilocus sequence typing, metalloregulatory proteins

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