THE ROLE OF ARGININE DEIMINASE FROM STREPTOCOCCUS PYOGENES IN INHIBITION MACROPHAGES NITROGEN MONOXIDE (NO) SYNTHESIS

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Abstract

The protective role of macrophages closely related to the production of bactericidal molecules, in which nitrogen monoxide (NO) play an  important role. Arginine serves as a substrate for inducible NO  synthase (iNOS) in course of NO production. Expression and activity  of iNOS are regulated by the availability of the substrate (arginine)  in the intercellular space. The bacterial enzyme arginine deiminase  also uses arginine as a substrate, causing its deficiency for host  cells. The aim of this study was to confirm the possible role of  arginine deiminase from S. pyogenes in inhibiting NO synthesis by  macrophages. For this purpose, a comparative study was made of  the effect on the synthesis of NO by macrophages of the products of  destruction of two strains: the initial S. pyogenes M49-16 and the  isogenic mutant S. pyogenes M49-16 delArcA with the inactivated  arginine deiminase gene (arcA). It has been shown that the ability of S. pyogenes M49-16 to inhibit production of NO by macrophages  depends on its arginine deiminase activity because the isogenous mutant of S. pyogenes M49-16 delArcA with the  inactivated gene arcA has lost its ability to inhibit NO synthesis. This allows us to consider the effects of S. pyogenes M49-16 as  effects of arginine deiminase. An analysis of the inhibitory mechanisms of the enzyme showed that suppression of NO synthesis was not associated with the effect of destruction products  of S. pyogenes M49-16 on the viability of macrophages. According to data of flow cytometry, incubation of cells in the presence of S.  pyogenes destruction products of the original and mutant strains did  not affect the level of iNOS expression, i.e. did not alter synthesis or  stability of this enzyme. At the same time, the decrease in NO  production under the influence of the original S. pyogenes strain  M49-16 correlated with a decrease in the content of arginine in the  culture medium. When exogenous arginine to the culture medium  was added, the effect of the original strain of the suppression of NO  production was declined. This confirms that the depletion of arginine  is the main mechanism of the inhibitory effect of arginine deiminase  on the production of NO by macrophages. The deficiency of NO  production in the course of streptococcal infection can lead to a  weakening of bactericidal activity of macrophages and to a decrease  in the effectiveness of antimicrobial protection.

About the authors

E. A. Starikova

Institute of Experimental Medicine

Author for correspondence.
Email: Starickova@yandex.ru

PhD (Biology), Senior Researcher, Department of Immunology,  Institute of Experimental Medicine, St. Petersburg, Russian Federation

197376, Russian Federation, St. Petersburg, Akademika Pavlova str., 12

Phone: +7 (812) 234-16-69 (office). Fax: +7 (812) 234-94-89

Россия

A. V. Sokolov

Institute of Experimental Medicine

Email: fake@neicon.ru

PhD, MD (Biology), Head of the Laboratory of Biochemical  Genetics, Department of Molecular Genetics, Institute of  Experimental Medicine, St. Petersburg, Russian Federation;  Professor of the Department of Fundamental Problems of  Medicine and Medical Technologies, St. Petersburg State University, St. Petersburg, Russian Federation

Россия

L. A. Burova

Institute of Experimental Medicine

Email: fake@neicon.ru

PhD, MD (Medicine), Leading Researcher, Department of  Molecular Genetics, Institute of Experimental Medicine, St. Petersburg, Russian Federation

Россия

A. S. Golovin

Institute of Experimental Medicine

Email: fake@neicon.ru

PhD Student, Department of Immunology, Institute of Experimental Medicine, St. Petersburg, Russian Federation

Россия

A. M. Lebedeva

Institute of Experimental Medicine

Email: fake@neicon.ru

PhD (Biology), Researcher, Department of Immunology,  Institute of Experimental Medicine, St. Petersburg, Russian Federation

Россия

V. B. Vasilyev

Institute of Experimental Medicine

St. Petersburg State University

Email: fake@neicon.ru

PhD, MD (Medicine), Head of the Department of Molecular  Genetics, Institute of Experimental Medicine, St.  Petersburg, Russian Federation; Professor of the  Department of Fundamental Problems of Medicine and  Medical Technologies, St. Petersburg State University, St. Petersburg, Russian Federation

Россия

I. S. Freidlin

Institute of Experimental Medicine

St. Petersburg State University

Email: fake@neicon.ru

PhD, MD (Medicine), Professor, RAS Corresponding Member, Main Researcher, Department of  Immunology, Institute of Experimental Medicine, St.  Petersburg, Russian Federation; Professor of the  Department of Fundamental Problems of Medicine and  Medical Technologies, St. Petersburg State University, St. Petersburg, Russian Federation

Россия

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Copyright (c) 2018 Starikova E.A., Sokolov A.V., Burova L.A., Golovin A.S., Lebedeva A.M., Vasilyev V.B., Freidlin I.S.

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