Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection

Eleonora Alexandrovna Starikova, Alexander Stanislavovich Golovin, Kirill Alexandrovich Vasilyev, Alena Borisovna Karaseva, Maria Konstantinovna Serebriakova, Alexey Victorovich Sokolov, Igor Vladimirovich Kudryavtsev, Larissa Alexandrovna Burova, Irina Vitalyevna Voynova, Alexander Nikolaevich Suvorov, Vadim Borisovich Vasilyev, Irina Solomonovna Freidlin

Research output

Abstract

Expression of gene of arginine deiminase (AD) allows adaptation of Streptococcus pyogenes to adverse environmental conditions. AD activity can lead to L-arginine deficiency in the host cells’ microenvironment. Bioavailability of L-arginine is an important factor regulating the functions of the immune cells in mammals. By introducing a mutation into S pyogenes M46-16, we obtained a strain with inactivated arcA/sagp gene (M49-16 delArcA), deficient in AD. This allowed elucidating the function of AD in pathogenesis of streptococcal infection. The virulence of the parental and mutant strains was examined in a murine model of subcutaneous streptococcal infection. L-arginine concentration in the plasma of mice infected with S pyogenes M49-16 delArcA remained unchanged in course of the entire experiment. At the same time mice infected with S pyogenes M49-16 demonstrated gradual diminution of L-arginine concentration in the blood plasma, which might be due to the activity of streptococcal AD. Mice infected with S pyogenes M49-16 delArcA demonstrated less intensive bacterial growth in the primary foci and less pronounced bacterial dissemination as compared with animals infected with the parental strain S pyogenes M46-16. Similarly, thymus involution, alterations in apoptosis, thymocyte subsets and Treg cells differentiation were less pronounced in mice infected with S pyogenes M49-16 delArcA than in those infected with the parental strain. The results obtained showed that S pyogenes M49-16 delArcA, unable to produce AD, had reduced virulence in comparison with the parental S pyogenes M49-16 strain. AD is an important factor for the realization of the pathogenic potential of streptococci.

Original languageEnglish
Article numbere12734
Number of pages11
JournalScandinavian Journal of Immunology
Volume89
Issue number2
DOIs
Publication statusPublished - 1 Feb 2019

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Streptococcus pyogenes
Atrophy
Infection
Arginine
Streptococcal Infections
Virulence
Cellular Microenvironment
Regulatory T-Lymphocytes
Thymocytes
arginine deiminase
Streptococcus
Thymus Gland
Biological Availability
Cell Differentiation
Mammals
Apoptosis
Gene Expression
Mutation
Growth
Genes

Scopus subject areas

  • Immunology

Cite this

Starikova, Eleonora Alexandrovna ; Golovin, Alexander Stanislavovich ; Vasilyev, Kirill Alexandrovich ; Karaseva, Alena Borisovna ; Serebriakova, Maria Konstantinovna ; Sokolov, Alexey Victorovich ; Kudryavtsev, Igor Vladimirovich ; Burova, Larissa Alexandrovna ; Voynova, Irina Vitalyevna ; Suvorov, Alexander Nikolaevich ; Vasilyev, Vadim Borisovich ; Freidlin, Irina Solomonovna. / Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection. In: Scandinavian Journal of Immunology. 2019 ; Vol. 89, No. 2.
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abstract = "Expression of gene of arginine deiminase (AD) allows adaptation of Streptococcus pyogenes to adverse environmental conditions. AD activity can lead to L-arginine deficiency in the host cells’ microenvironment. Bioavailability of L-arginine is an important factor regulating the functions of the immune cells in mammals. By introducing a mutation into S pyogenes M46-16, we obtained a strain with inactivated arcA/sagp gene (M49-16 delArcA), deficient in AD. This allowed elucidating the function of AD in pathogenesis of streptococcal infection. The virulence of the parental and mutant strains was examined in a murine model of subcutaneous streptococcal infection. L-arginine concentration in the plasma of mice infected with S pyogenes M49-16 delArcA remained unchanged in course of the entire experiment. At the same time mice infected with S pyogenes M49-16 demonstrated gradual diminution of L-arginine concentration in the blood plasma, which might be due to the activity of streptococcal AD. Mice infected with S pyogenes M49-16 delArcA demonstrated less intensive bacterial growth in the primary foci and less pronounced bacterial dissemination as compared with animals infected with the parental strain S pyogenes M46-16. Similarly, thymus involution, alterations in apoptosis, thymocyte subsets and Treg cells differentiation were less pronounced in mice infected with S pyogenes M49-16 delArcA than in those infected with the parental strain. The results obtained showed that S pyogenes M49-16 delArcA, unable to produce AD, had reduced virulence in comparison with the parental S pyogenes M49-16 strain. AD is an important factor for the realization of the pathogenic potential of streptococci.",
keywords = "Animals, Apoptosis, Arginine/metabolism, Atrophy, Bacterial Proteins/genetics, Cell Differentiation, Cells, Cultured, Disease Models, Animal, Humans, Hydrolases/genetics, Mice, Mice, Inbred C57BL, Mice, Inbred CBA, Mutagenesis, Site-Directed, Mutation/genetics, Streptococcal Infections/immunology, Streptococcus pyogenes/pathogenicity, T-Lymphocytes/physiology, Thymus Gland/pathology, Virulence, SYSTEM, APOPTOSIS, INDUCTION, VIRUS INFECTION, REGULATORY T-CELLS, MICE, THYMOCYTES, PROTEINS, EXPRESSION",
author = "Starikova, {Eleonora Alexandrovna} and Golovin, {Alexander Stanislavovich} and Vasilyev, {Kirill Alexandrovich} and Karaseva, {Alena Borisovna} and Serebriakova, {Maria Konstantinovna} and Sokolov, {Alexey Victorovich} and Kudryavtsev, {Igor Vladimirovich} and Burova, {Larissa Alexandrovna} and Voynova, {Irina Vitalyevna} and Suvorov, {Alexander Nikolaevich} and Vasilyev, {Vadim Borisovich} and Freidlin, {Irina Solomonovna}",
year = "2019",
month = "2",
day = "1",
doi = "10.1111/sji.12734",
language = "English",
volume = "89",
journal = "Scandinavian Journal of Immunology",
issn = "0300-9475",
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Starikova, EA, Golovin, AS, Vasilyev, KA, Karaseva, AB, Serebriakova, MK, Sokolov, AV, Kudryavtsev, IV, Burova, LA, Voynova, IV, Suvorov, AN, Vasilyev, VB & Freidlin, IS 2019, 'Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection', Scandinavian Journal of Immunology, vol. 89, no. 2, e12734. https://doi.org/10.1111/sji.12734

Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection. / Starikova, Eleonora Alexandrovna; Golovin, Alexander Stanislavovich; Vasilyev, Kirill Alexandrovich; Karaseva, Alena Borisovna; Serebriakova, Maria Konstantinovna; Sokolov, Alexey Victorovich; Kudryavtsev, Igor Vladimirovich; Burova, Larissa Alexandrovna; Voynova, Irina Vitalyevna; Suvorov, Alexander Nikolaevich; Vasilyev, Vadim Borisovich; Freidlin, Irina Solomonovna.

In: Scandinavian Journal of Immunology, Vol. 89, No. 2, e12734, 01.02.2019.

Research output

TY - JOUR

T1 - Role of arginine deiminase in thymic atrophy during experimental Streptococcus pyogenes infection

AU - Starikova, Eleonora Alexandrovna

AU - Golovin, Alexander Stanislavovich

AU - Vasilyev, Kirill Alexandrovich

AU - Karaseva, Alena Borisovna

AU - Serebriakova, Maria Konstantinovna

AU - Sokolov, Alexey Victorovich

AU - Kudryavtsev, Igor Vladimirovich

AU - Burova, Larissa Alexandrovna

AU - Voynova, Irina Vitalyevna

AU - Suvorov, Alexander Nikolaevich

AU - Vasilyev, Vadim Borisovich

AU - Freidlin, Irina Solomonovna

PY - 2019/2/1

Y1 - 2019/2/1

N2 - Expression of gene of arginine deiminase (AD) allows adaptation of Streptococcus pyogenes to adverse environmental conditions. AD activity can lead to L-arginine deficiency in the host cells’ microenvironment. Bioavailability of L-arginine is an important factor regulating the functions of the immune cells in mammals. By introducing a mutation into S pyogenes M46-16, we obtained a strain with inactivated arcA/sagp gene (M49-16 delArcA), deficient in AD. This allowed elucidating the function of AD in pathogenesis of streptococcal infection. The virulence of the parental and mutant strains was examined in a murine model of subcutaneous streptococcal infection. L-arginine concentration in the plasma of mice infected with S pyogenes M49-16 delArcA remained unchanged in course of the entire experiment. At the same time mice infected with S pyogenes M49-16 demonstrated gradual diminution of L-arginine concentration in the blood plasma, which might be due to the activity of streptococcal AD. Mice infected with S pyogenes M49-16 delArcA demonstrated less intensive bacterial growth in the primary foci and less pronounced bacterial dissemination as compared with animals infected with the parental strain S pyogenes M46-16. Similarly, thymus involution, alterations in apoptosis, thymocyte subsets and Treg cells differentiation were less pronounced in mice infected with S pyogenes M49-16 delArcA than in those infected with the parental strain. The results obtained showed that S pyogenes M49-16 delArcA, unable to produce AD, had reduced virulence in comparison with the parental S pyogenes M49-16 strain. AD is an important factor for the realization of the pathogenic potential of streptococci.

AB - Expression of gene of arginine deiminase (AD) allows adaptation of Streptococcus pyogenes to adverse environmental conditions. AD activity can lead to L-arginine deficiency in the host cells’ microenvironment. Bioavailability of L-arginine is an important factor regulating the functions of the immune cells in mammals. By introducing a mutation into S pyogenes M46-16, we obtained a strain with inactivated arcA/sagp gene (M49-16 delArcA), deficient in AD. This allowed elucidating the function of AD in pathogenesis of streptococcal infection. The virulence of the parental and mutant strains was examined in a murine model of subcutaneous streptococcal infection. L-arginine concentration in the plasma of mice infected with S pyogenes M49-16 delArcA remained unchanged in course of the entire experiment. At the same time mice infected with S pyogenes M49-16 demonstrated gradual diminution of L-arginine concentration in the blood plasma, which might be due to the activity of streptococcal AD. Mice infected with S pyogenes M49-16 delArcA demonstrated less intensive bacterial growth in the primary foci and less pronounced bacterial dissemination as compared with animals infected with the parental strain S pyogenes M46-16. Similarly, thymus involution, alterations in apoptosis, thymocyte subsets and Treg cells differentiation were less pronounced in mice infected with S pyogenes M49-16 delArcA than in those infected with the parental strain. The results obtained showed that S pyogenes M49-16 delArcA, unable to produce AD, had reduced virulence in comparison with the parental S pyogenes M49-16 strain. AD is an important factor for the realization of the pathogenic potential of streptococci.

KW - Animals

KW - Apoptosis

KW - Arginine/metabolism

KW - Atrophy

KW - Bacterial Proteins/genetics

KW - Cell Differentiation

KW - Cells, Cultured

KW - Disease Models, Animal

KW - Humans

KW - Hydrolases/genetics

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Inbred CBA

KW - Mutagenesis, Site-Directed

KW - Mutation/genetics

KW - Streptococcal Infections/immunology

KW - Streptococcus pyogenes/pathogenicity

KW - T-Lymphocytes/physiology

KW - Thymus Gland/pathology

KW - Virulence

KW - SYSTEM

KW - APOPTOSIS

KW - INDUCTION

KW - VIRUS INFECTION

KW - REGULATORY T-CELLS

KW - MICE

KW - THYMOCYTES

KW - PROTEINS

KW - EXPRESSION

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DO - 10.1111/sji.12734

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VL - 89

JO - Scandinavian Journal of Immunology

JF - Scandinavian Journal of Immunology

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