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

Cover Page


Cite item

Full Text

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

Russian Federation

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

Russian Federation

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

Russian Federation

A. S. Golovin

Institute of Experimental Medicine

Email: fake@neicon.ru

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

Russian Federation

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

Russian Federation

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

Russian Federation

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

Russian Federation

References

  1. Головин А.С., Старикова Э.А., Фрейдлин И.С. Влияние аргининдеиминазы Streptococus pyogenes на бактерицидную активность макрофагов // Медицинский академический журнал. 2016. Т. 16, № 4. С. 152. [Golovin A.S., Starikova E.A., Freidlin I.S. Effect of arginine deiminase from Streptococcus pyogenes on the bactericidal activity of macrophages. Meditsinskii akademicheskii zhurnal = Medical Aсademical Journal, 2016, vol. 16, no. 4, p. 152. (In Russ.)]
  2. Старикова Э.А., Карасева А.Б., Бурова Л.А., Суворов А.Н., Соколов А.В., Васильев В.Б., Фрейдлин И.С. Роль аргининдеиминазы Streptococcus pyogenes M49-16 в ингибиции пролиферации эндотелиальных клеток человека линии EA.hy926 // Медицинская иммунология. 2016. Т. 18, № 6. C. 559–566. [Starikova E.A., Karaseva A.B., Burova L.A., Suvorov A.N., Sokolov A.V., Vasilyev V.B., Freidlin I.S. A role of arginine deiminase from streptococcus pyogenes M49-16 in promoting infection and inhibition of endothelial cell proliferation. Meditsinskaya immunologiya = Medical Immunology (Russia), 2016, vol. 18, no. 6, pp. 555–562. doi: 10.15789/1563-0625-2016-6-555-562 (In Russ.)]
  3. Abdelal A.T. Arginine catabolism by microorganisms. Annual Rev. Microbiol., 1979, vol. 33, no. 1, pp. 139–168. doi: 10.1146/annurev.mi.33.100179.001035
  4. Barnett T.C., Liebl D., Seymour L.M., Gillen Ch.M., Lim J.Y., LaRock Ch.N., Davies M.R., Schulz B.L., Nizet V., Teasdale R.V., Walker M.J. The globally disseminated M1T1 clone of group A streptococcus evades autophagy for intracellular replication. Cell Host Microbe, 2013, vol. 14, iss. 6, pp. 675–682. doi: 10.1016/j.chom.2013.11.003
  5. Basma H., Norrby-Teglund A., Guedez Y., McGeer A., Low D.E., El-Ahmedy O., Schwartz B., Kotb M. Risk factors in the pathogenesis of invasive group A streptococcal infections: role of protective humoral immunity. Infect. Immun., 1999, vol. 67, no. 4, pp. 1871–1877.
  6. Bastiat-Sempe B., Love J.F., Lomayesva N., Wessels M.R. Streptolysin O and NAD-glycohydrolase prevent phagolysosome acidification and promote group A Streptococcus survival in macrophages. MBio, 2014, vol. 5, no. 5, pp. 1–11. doi: 10.1128/mBio.01690-14
  7. Bronte V., Zanovello P. Regulation of immune responses by L-arginine metabolism. Nat. Rev. Immunol., 2005, vol. 5, pp. 641–654. doi: 10.1038/nri1668
  8. Cotter P.D., Hill C. Surviving the acid test: responses of gram-positive bacteria to low pH. Microbiol. Mol. Biol. Rev., 2003, vol. 67, no. 3, pp. 429–453. doi: 10.1128/MMBR.67.3.429-453.2003
  9. Cusumano Z.T., Watson M.E., Caparon M.G. Streptococcus pyogenes arginine and citrulline catabolism promotes infection and modulates innate immunity. Infect. Immun., 2014, vol. 82, no. 1, pp. 233–242. doi: 10.1128/IAI.00916-13
  10. Das P., Lahiri A., Chakravortty D. Modulation of the arginase pathway in the context of microbial pathogenesis: a metabolic enzyme moonlighting as an immune modulator. PLoS Pathog., 2010, vol. 6, iss. 6: e1000899. doi: 10.1371/journal.ppat.1000899
  11. Goldmann O., von Kockritz-Blickwede M., Holtje C., Chhatwal G.S., Geffers R., Medina E. Transcriptome analysis of murine macrophages in response to infection with streptococcus pyogenes reveals an unusual activation program. Infect. Immun., 2007, vol. 75, no. 8, pp. 4148–4157. doi: 10.1128/IAI.00181-07
  12. Goldmann O., Rohde M., Chhatwal G.S., Medina E. Role of macrophages in host resistance to group a streptococci. Infect. Immun., 2004, vol. 72, no. 5, pp. 2956–2963. doi: 10.1128/IAI.72.5.2956-2963.2004
  13. Lin A.E., Beasley F.C., Keller N., Hollands A., Urbano R., Troemel E.R., Hoffman H.M., Nizet V. A group A Streptococcus ADP-ribosyltransferase toxin stimulates a protective interleukin 1β-dependent macrophage immune response. MBio, 2015, vol. 6, no. 2, pp. 1–12. doi: 10.1128/mBio.00133-15
  14. Lu S.-L., Kuo C.-F., Chen H.-W., Yang Y.-S., Liu C.-C., Anderson R., Wu J.-J., Lin Y.-S. Insufficient acidification of autophagosomes facilitates group a streptococcus survival and growth in endothelial cells. MBio, 2015, vol. 6, no. 5, pp. 1–12. doi: 10.1128/mBio.01435-15
  15. Mishalian I., Ordan M., Peled A., Maly A., Eichenbaum M.B., Ravins M., Aychek T., Jung S., Hanski E. Recruited macrophages control dissemination of group A Streptococcus from infected soft tissues. J. Immunol., 2011, vol. 187, iss. 11, pp. 6022–6031. doi: 10.4049/jimmunol.1101385
  16. Mori M. Regulation of nitric oxide synthesis and apoptosis by arginase and arginine recycling. J. Nutr., 2007, vol. 137, iss. 6, pp. 1616S–1620S.
  17. Nathan C., Shiloh M.U. Reactive oxygen and nitrogen intermediates in the relationship between mammalian hosts and microbial pathogens. Proc. Natl. Acad. Sci. USA, 2000, vol. 97, no. 16, pp. 8841–8848. doi: 10.1073/pnas.97.16.8841
  18. Noh E.J., Kang S.W., Shin Y.J., Kim D.C., Park I.S., Kim M.Y., Chun B.G., Min B.H. Characterization of mycoplasma arginine deiminase expressed in E. coli and its inhibitory regulation of nitric oxide synthesis. Mol. Cells, 2002, vol. 13, no. 1, pp. 137–143.
  19. O’Neill A.M., Thurston T.L.M., Holden D.W. Cytosolic replication of group A streptococcus in human macrophages. MBio, 2016, vol. 7, no. 2, pp. 1–16. doi: 10.1128/mBio.00020-16
  20. Pautz A., Art J., Hahn S., Nowag S., Voss C., Kleinert H. Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide, 2010, vol. 23, no. 2, pp. 75–93. doi: 10.1016/j.niox.2010.04.007
  21. Sakurai A., Maruyama F., Funao J., Nozawa T., Aikawa Ch., Okahashi N., Shintani S., Hamada Sh., Ooshima T., Nakagawa I. Specific behavior of intracellular streptococcus pyogenes that has undergone autophagic degradation is associated with bacterial streptolysin O and host small G proteins Rab5 and Rab7. J. Biol. Chem., 2010, vol. 285, no. 29, pp. 22666–22675. doi: 10.1074/jbc.M109.100131
  22. Shen L-J., Lin W.C., Beloussow K., Hosoya K., Terasaki T., Ann D.K., Shen W.C. Recombinant arginine deiminase as a differential modulator of inducible (iNOS) and endothelial (eNOS) nitric oxide synthetase activity in cultured endothelial cells. Biochem. Pharmacol., 2003, vol. 66, no. 10, pp. 1945–1952. doi: 10.1016/S0006-2952(03)00555-0
  23. Timmer A.M., Timmer J.C., Pence M.A., Hsu L.-C., Ghochani M., Frey T.G., Karin M., Salvesen G.S., Nizet V. Streptolysin O promotes group A streptococcus immune evasion by accelerated macrophage apoptosis. J. Biol. Chem., 2009, vol. 284, no. 2, pp. 862–871. doi: 10.1074/jbc.M804632200
  24. Wang H., Liang X.H., Zhao R.X., Feng L.D., Li H. Spectrophotometer determination of arginine in grape juice using 8-hydroquinoline. Agr. Sci. China, 2008, vol. 7, no. 10, pp. 1210–1215. doi: 10.1016/S1671-2927(08)60166-2

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

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

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 64788 от 02.02.2016.


This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies