Characterization of toxigenic Corynebacterium diphtheriae strains isolated in Russia

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Abstract

The aim of the study was to characterize toxigenic strains of Corynebacterium diphtheriae by examining 12 toxigenic strains of C. diphtheriae isolated in Russia between January, 2017 to June, 2019. The morphological, toxigenic and biochemical properties of C. diphtheriae was studied. Genotyping of C. diphtheriae strains was performed using MLST and dtxR gene sequencing with subsequent phylogenetic analysis. Results. Toxigenic strains of C. diphtheriae were isolated in the Novosibirsk, Samara and Chelyabinsk Regions, the Khanty-Mansi Autonomous Okrug — Yugra as well as the Republic of Northern Ossetia — Alania. Among these strains, 5 were isolated from diphtheria patients (moderate disease found in one case, mild course — remaining patients) and 7 strains were isolated from bacterial carriers. In two cases C. diphtheriae from diphtheria patients were identified as ST25 sequence type, gravis variant; in one case — ST8 type, gravis variant; two cases — ST67 sequence type, mitis variant. In asymptomatic carriers of tox-positive C. diphtheriae strains they belonged to ST25 sequence type, gravis variant — in two cases, ST67 type, mitis variant — in four cases. A sequencing type was not identified in one case. All sequence types were widespread globally being presented by a large number of isolates in the PubMLST and characterized by a substantial amount of derivative sequence types. At the same time, they belonged to different clonal complexes and differed markedly from each other contributing to their reliable difference as assessed by MLST. Study of gene dtxR sequence diversity showed that all allelic variants were typical for the representatives of these sequence types. New alleles of gene dtxR were not revealed in strains examined. It was shown that non-synonymous substitution C440T leading to A147V amino acid substitution was found solely in one allele distributed in ST8, ST185, ST195 and ST451 types suggesting at late mutation. In contrast, the polymorphism C640A resulting in the amino acid substitution L214I was found not only in the same allele, but also in the basal tree branches indicating that isoleucine was in the ancestral sequence of the protein.

About the authors

O. Yu. Borisova

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology; Russian National Research Medical University named after N.I. Pirogov

Author for correspondence.
Email: olgborisova@mail.ru
ORCID iD: 0000-0001-6316-5046

Olga Yu. Borisova,  PhD, MD (Medicine), Professor, Head of the Laboratory of Diagnostic of Diphtheria and Pertussis Infections; Professor of the Department of Microbiology and Virology 

125212, Moscow, Admiral Makarov str., 10

Phone: +7 (906) 747-64-84 (office), 8 (916) 147-19-60 (mobile) 

Russian Federation

N. T. Gadua

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology

Email: 8nati8@mail.ru
ORCID iD: 0000-0001-6247-6176

PhD (Medicine), Senior Researcher, Laboratory of Diagnostic of Diphtheria and Pertussis Infections 

Moscow

Russian Federation

A. S. Pimenova

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology

Email: alenaa_85@mail.ru
ORCID iD: 0000-0002-6914-3531

PhD (Medicine), Senior Researcher, Laboratory of Diagnostic of Diphtheria and Pertussis Infections 

Moscow

Russian Federation

A. V. Chaplin

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology; Russian National Research Medical University named after N.I. Pirogov

Email: okolomedik@gmail.com
ORCID iD: 0000-0003-1377-7153

PhD (Medicine), Researcher, Laboratory of Diagnostic of Diphtheria and Pertussis Infections; Associate Professor, Department of Microbiology and Virology 

Moscow

Russian Federation

I. A. Chagina

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology

Email: skaller84@mail.ru
ORCID iD: 0000-0003-2867-9548

PhD (Medicine), Senior Researcher, Laboratory of Diagnostic of Diphtheria and Pertussis Infections 

Moscow

Russian Federation

Y. N. Urban

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology

Email: urbanek@mail.ru

PhD (Biology), Senior Researcher, Laboratory of Clinical Microbiology and Biotechnology 

Moscow

Russian Federation

N. M. Maksimova

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology

Email: 4592146@mail.ru
ORCID iD: 0000-0001-5057-4318

PhD, MD (Medicine), Head Researcher, Laboratory of Epidemiological Surveillance for Diphtheria and Pertussis 

Moscow

Russian Federation

M. P. Korzhenkova

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology

Email: 4592146@mail.ru

PhD (Medicine), Leading Researcher, Laboratory of Epidemiological Surveillance for Diphtheria and Pertussis 

Moscow

Russian Federation

S. S. Afanasiev

G.N. Gabrichevsky Research Institute for Epidemiology and Microbiology

Email: afanasievss409.4@bk.ru
ORCID iD: 0000-0001-6497-1795

PhD, MD (Medicine), Head Researcher 

Moscow

Russian Federation

L. I. Kafarskaya

I.M. Sechenov First Moscow State Medical University

Email: likmed@mail.ru
ORCID iD: 0000-0002-5488-5786

PhD, MD (Medicine), Professor, Head of the Department of Microbiology and Virology 

Moscow

Russian Federation

M. S. Afanasyev

I.M. Sechenov First Moscow State Medical University

Email: mafa78@inbox.ru
ORCID iD: 0000-0003-4061-1407

PhD, MD (Medicine), Professor, Department of Clinical Allergology and Immunology 

Moscow

Russian Federation

V. V. Krikun

Nizhnevartovsk District Clinical Children’s Hospital

Email: uodb@odbhmao.ru

Head of the Bacteriological Laboratory 

Nizhnevartovsk

Russian Federation

O. Yu. Yakunina

Center of Hygiene and Epidemiology in Novosibirsk Region

Email: olgacgie@mail.ru

Head of the Bacteriological Laboratory 

Novosibirsk

Russian Federation

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Copyright (c) 2020 Borisova O.Y., Gadua N.T., Pimenova A.S., Chaplin A.V., Chagina I.A., Urban Y.N., Maksimova N.M., Korzhenkova M.P., Afanasiev S.S., Kafarskaya L.I., Afanasyev M.S., Krikun V.V., Yakunina O.Y.

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