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Scand J Immunol ; 89(2): e12734, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30471128

RESUMO

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.


Assuntos
Proteínas de Bactérias/metabolismo , Hidrolases/metabolismo , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/fisiologia , Linfócitos T/fisiologia , Timo/patologia , Animais , Apoptose , Arginina/metabolismo , Atrofia , Proteínas de Bactérias/genética , Diferenciação Celular , Células Cultivadas , Modelos Animais de Doenças , Humanos , Hidrolases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Mutagênese Sítio-Dirigida , Mutação/genética , Infecções Estreptocócicas/imunologia , Streptococcus pyogenes/patogenicidade , Virulência
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