Biological properties of М. tuberculosis and the system of proteinase/inhibitor in the pathogenesis of experimental nephrotuberculosis



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Abstract

Relevance. Progressive kidney damage is reduced to tubulointerstitial diseases characterized by atrophy and hypoxia of the tubules, damage to peritubular capillaries and interstitial fibrosis. Aim. To assess the effect of biological properties of M. tuberculosis (MBT) on the proteinase/inhibitor system of blood and structural features of the renal parenchyma in the pathogenesis of experimental nephrotuberculosis (NT). Material and methods. The bacterial DNA was submitted to whole genome sequencing on the DNBSEQ-G50 platform followed by bioinformatics analysis using SAM-TB, Geneious R, SIFT, PAM1).  NT was modeled on 60 sexually mature male rabbits of the Soviet Chinchilla breed, by introducing a suspension of the drug-sensitive (DS) international reference strain H37Rv (group 1) and drug-resistant (DR) clinical Beijing genotype strain 5582 (group 2) into the cortex of the parenchyma of kidney. The blood levels of neutrophil elastase (NE), matrix metalloproteinases-1 and -9 (MMP), tissue inhibitor of metalloproteinase-1 (TIMP-1), cystatin C, creatinine (CR), urea, albumin (AL), ceruloplasmin (CP), and adenosinedeaminase (ADA) were measured at baseline and after 2.5 and 22 weeks. Morphological changes in the structural components of the nephron were assessed after 22 weeks. Results. After 2.5 weeks, group 1 differed from group 2 in the increased concentrations of MMP-1, MMP-9, and cystatin C (p=0.02). After 22 weeks, in group 1, compared with group 2, the levels of MMP-9 and CP increased, while TIMP-1, cystatin C, and AL decreased (p=0.02). At all times in both groups, the levels of NE, CP and ADA remained elevated, while urea and CR did not change. In group 1, compared with group 2, the area of specific inflammation was larger and the severity of fibrotic changes was less (p=0.02). When infected with the strain of DS MBT, NT is characterized by a predominance of non-specific changes, contrasting with a predominantly productive reaction and fibrosis with a DR strain infection. Conclusion. Differences in the proteinase / inhibitor system in blood and structural changes in the kidneys in the pathogenesis of the experimental NT, caused by genetically and phenotypically different strains H37RV and Beijing 5582, have been established. Features of the development of the pathological process can be associated with the identified significant mutations in the the ramB, perM, fadE15 genes strains Beijing 5582.

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Dilyara Esmedlyaeva

State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian, St. Petersburg

Author for correspondence.
Email: diljara-e@yandex.ru
ORCID iD: 0000-0002-9841-0061
SPIN-code: 9402-4487

PhD (Biology), Senior Researcher of the Research Laboratory of Microbiology, Biochemistry and Immunogenetics 

Russian Federation, Ligovsky ave., 2-4, St. Petersburg, 191036, Russian Federation

Igor Mokrousov

Pasteur Research Institute of Epidemiology and Microbiology

Email: imokrousov@mail.ru
ORCID iD: 0000-0001-5924-0576
SPIN-code: 7879-6893

D.Sc. (Biology), Head of Laboratory of Molecular Epidemiology and Evolutionary Genetics

197101, Saint-Petersburg, 14, st. Mira,

Anna Vyazovaya

Pasteur Research Institute of Epidemiology and Microbiology,Saint-Petersburg

Email: annavyazovaya@gmail.com
ORCID iD: 0000-0001-9140-8957
SPIN-code: 1101-8060

D.Sc. (Biology), Leading researcher, Laboratory of Molecular Epidemiology and Evolutionary Genetics

Russian Federation, 197101 Saint-Petersburg st. Mira 14

Dmitrii Polev

Pasteur Research Institute of Epidemiology and Microbiology, Saint-Petersburg

Email: brantoza@gmail.com
ORCID iD: 0000-0001-9679-2791
SPIN-code: 9861-1284

PhD (Biology), Head of Metagenomics research group

Russian Federation, 197101,Saint-Petersburg st. Mira 14

Natalia Blum

Kirov Military medical academy, St. Petersburg

Email: blumn@mail.ru
ORCID iD: 0000-0003-1445-6714
SPIN-code: 4492-6190

Senior teacher of the department рathological anatomy

Russian Federation, 194044, St. Petersburg194044, Academician Lebedev street, 6Zh

Nina Alekseeva

St. Petersburg Saint-Petersburg State University

Email: ninaalexeyeva@mail.ru
ORCID iD: 0000-0001-8837-6739
SPIN-code: 2478-2746

PhD (Physics), Senior Researcher of Scientific Technical Information Department

Russian Federation, 199034, St Petersburg Universitetskaya Embankment 7-9

Marina Dyakova

State Research Institute of Phthisiopulmonology of the Ministry of Healthcare of the Russian, St. Petersburg

Email: marinadyakova@yandex.ru
ORCID iD: 0000-0002-7810-880X
SPIN-code: 7858-4573

D. Sc. (Biology),senior researcher at the laboratory of microbiology, biochemistry and immunogenetics

191036, St. Petersburg, Ligovsky pr. 2-4

Marine Dogonadze

State Research Institute of Phthisiopulmonology of the Ministry of the Ministry of Health of Russia

Email: marine-md@mail.ru
ORCID iD: 0000-0002-9161-466X
SPIN-code: 7475-9828

Candidate of Biological Sciences, Senior Researcher of the Research Laboratory of Microbiology, Biochemistry and Immunogenetics of the St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian

 

 

 

Federation. Candidate of Biological Sciences. 

Ligovsky ave., 2-4, St. Petersburg, 191036, Russian Federation

Boris Ariel

State Research Institute of Phthisiopulmonology of the Ministry of the Ministry of Health of Russia

Email: arielboris@rambler.ru
ORCID iD: 0000-0002-7243-8621
SPIN-code: 6699-6152

Doctor of Medical Sciences, Professor ,Advisor to the Director of the St. Petersburg Research Institute of Phthisiopulmonology

Ligovsky ave., 2-4, St. Petersburg, 191036, Russian Federation

Tatyana Vinogradova

State Research Institute of Phthisiopulmonology of the Ministry of the Ministry of Health of Russia

Email: vinogradova@spbniif.ru
ORCID iD: 0000-0002-5234-349X
SPIN-code: 6354-5070

Doctor of Medical Sciences, Professor, Head of the Research Laboratory of Experimental Medicine of the St. Petersburg Research Institute of Phthisiopulmonology 

Ligovsky ave., 2-4, St. Petersburg, 191036, Russian Federation

Petr Yablonskiy

State Research Institute of Phthisiopulmonology of the Ministry of the Ministry of Health of Russia
St. Petersburg State University, Russian Federation

Email: piotr_yablonskii@mail.ru
ORCID iD: 0000-0003-4385-9643
SPIN-code: 3433-2624

Doctor of Medical Sciences, Professor, Director of the St. Petersburg Research Institute of Phthisiopulmonology of the Ministry of Health of the Russian Federation; 

Doctor of Medical Sciences, Professor, First Vice-Rector for Medical Activities of St. Petersburg State University.

Ligovsky ave., 2-4, St. Petersburg, 191036, Russian Federation Universitetskaya nab., 7/9, St. Petersburg, 199034, Russian Federation

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