In vivo virulence of Beijing genotype Mycobacterium tuberculosis

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Abstract

Mycobacterium tuberculosis Beijing genotype strains comprise 50–80% in Russian Federation, which are divided into the main B0/W148, CladeA, and CAO clusters based on VNTR and SNP analysis. It should be noted that such phylogenetically highly close MTB strains belong to the modern Beijing family, generally demonstrating high transmissibility, association with drug resistance, and prevalence among patients with severe forms of the disease. However, studies on MTB genetic cluster strain-related virulence are scarce and contradictory. Here, we investigated virulence of diverse Mycobacterium tuberculosis strains belonging to the B0/W148, CladeA and CAO clusters and nonclustered strain NK of the Beijing family as well as laboratory strain H37Rv in C57BL/6 mice. It was found that mice infected with NK and B0/W148 vs. CladeA strains revealed the peak and the lowest mortality, respectively, while assessing survival rate in various groups (20 mice per MTB strain examined). Analyzing experimental data in mice demonstrated that all MTB strains were able to cause typical tuberculosis-related pathogenic signs. In particular, time-dependent evaluation of pathological changes (on 1, 3, 7, 14, 21, 28, 60 and 120 day post infection) in the lungs and spleen revealed significant differences among various strains. Tuberculosis progression was observed in the mice infected with B0/W148 and NK strains, whereas CladeA, CAO and H37Rv strains resulted in stabilized course and less marked organs damage. Moreover, we found that bacterial load after infection with Beijing family clustering strains was lower compared to that of the reference H37Rv strain, except NK strain demonstrating the peak bacterial load among the Beijing family comparable to H37Rv strain at 120 dpi. Thus, it was found that the level of virulence between most virulent B0/W148 cluster strain vs. NK strain was similar. Overall, the data obtained indicate that Beijing genotype strains are characterized by a diverse range of phenotypic virulence in vivo.

About the authors

J. A. Bespyatykh

Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency

Email: juliabespyatykh@gmail.com
ORCID iD: 0000-0002-4408-503X

Julia A. Bespyatykh - PhD (Biology), Researcher, Laboratory of Molecular Genetics of Microorganisms, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency.

119435, Moscow, Malaya Pirogovskaya str., 1a.

Phone: +7 (909) 961-18-46. Fax: +7 (499) 246-44-09.

Russian Federation

Т. I. Vinogradova

St. Petersburg Research Institute of Phthisiopulmonology

Email: fake@neicon.ru

PhD, MD (Medicine), Professor, Head Researcher, St. Petersburg State Research Institute of Phthisiopulmonology.

St. Petersburg.

Russian Federation

O. A. Manicheva

St. Petersburg Research Institute of Phthisiopulmonology

Email: fake@neicon.ru

PhD, MD (Biology), Leading Researcher, St. Petersburg State Research Institute of Phthisiopulmonology.

St. Petersburg.

Russian Federation

N. V. Zabolotnykh

St. Petersburg Research Institute of Phthisiopulmonology

Email: fake@neicon.ru

PhD, MD (Medicine), Leading Researcher, St. Petersburg State Research Institute of Phthisiopulmonology.

St. Petersburg.

Russian Federation

M. Z. Dogonadze

St. Petersburg Research Institute of Phthisiopulmonology

Email: fake@neicon.ru

PhD (Biology), Senior Researcher, St. Petersburg State Research Institute of Phthisiopulmonology.

St. Petersburg.

Russian Federation

M. L. Vitovskaya

St. Petersburg Research Institute of Phthisiopulmonology

Email: fake@neicon.ru

PhD (Medicine), Senior Researcher, St. Petersburg State Research Institute of Phthisiopulmonology.

St. Petersburg.

Russian Federation

A. S. Guliaev

Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency

Email: fake@neicon.ru

PhD (Biology), Junior Researcher, Laboratory of Molecular Genetics of Microorganisms, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency.

Moscow.

Russian Federation

V. Yu. Zhuravlev

St. Petersburg Research Institute of Phthisiopulmonology

Email: fake@neicon.ru

PhD (Medicine), Leading Researcher, St. Petersburg State Research Institute of Phthisiopulmonology.

St. Petersburg.

Russian Federation

E. A. Shitikov

Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency

Email: fake@neicon.ru

PhD (Biology), Head of the Laboratory of Molecular Genetics of Microorganisms, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency.

Moscow.

Russian Federation

E. N. Ilina

Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency

Author for correspondence.
Email: fake@neicon.ru

PhD, MD (Biology), RAS Professor, Deputy Director for Science, Federal Research and Clinical Center of Physical-Chemical Medicine of Federal Medical Biological Agency.

Moscow.

Russian Federation

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Copyright (c) 2019 Bespyatykh J.A., Vinogradova Т.I., Manicheva O.A., Zabolotnykh N.V., Dogonadze M.Z., Vitovskaya M.L., Guliaev A.S., Zhuravlev V.Y., Shitikov E.A., Ilina E.N.

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