Streptococcus pyogenes: phenomenon of nonimmune binding of human immunoglobulins and its role in pathology

M and M-like proteins represent the main pathogenicity factors of Streptococcus pyogenes, a widely spread and potentially lethal bacterial pathogen. These proteins provide resistance of the microbe to innate and adaptive immune response, due to attraction of specific human proteins to the streptococcal surface. Nonimmune binding of immunoglobulins G (IgG) and A (IgA) via their Fc domains to M and M-like proteins was described over 40 years ago, but its role for the pathogenicity of Streptococcus pyogenes is far from definite resolution. The discovery of this phenomenon should be considered among quite significant achievements of modern microbiology, since it had a huge impact upon development of innovative approaches, technologies and tools for microbiological, immunological and molecular diagnostics. It also promoted fundamental studies in pathogenesis of distinct infectious states and their complications caused by S. pyogenes. The non-immune binding of host immunoglobulins was previously suggested to be important mainly in immune conditions on the surface of mucous membranes and their secretions, but not in blood plasma, whereas other studies have pointed to significance of this phenomenon in protecting microbes from phagocytosis in non-immune blood of the host. It was also shown that the effect of Fc-binding causes increased pathogenicity of streptococci both in primary focus of infection, and during chronical course of the process, thus contributing to development of autoimmune diseases caused by S. pyogenes infection and leading to tissue damage in experimental animals. The experimental autoimmune process can be prevented by administering purified Fc fragments of immunoglobulins to the animals, blocking this process at the early stages of its development. A significant place in pathogenesis of IgA nephropathy (IgAN) belongs to streptococcal diseases. IgAN has been described as a mesangial proliferative process, due to initial IgA-Fcα deposition in renal mesangium cells. The data from literature describe successful modeling of individual IgAN traits, and expand our understanding of pathogenic properties and functions of Fcα binding receptor M proteins of S. pyogenes. The data reviewed in the article also presume the relevance of recently proposed ideas about an important role of non-immune Ig binding in streptococcal diseases, even in cases that differ in their development mechanism. These studies, including possible search for tools and techniques of preventive and potentially therapeutic applications, require additional efforts to study the binding of Fc fragments of IgG and IgA to M and M-like proteins of Streptococcus pyogenes

Story-“Record” vs Spontaneous Narrative in Light of a Comparative Analysis of Linguistic Feature

A memoir-type narrative as a structured text in a certain way, represented by at least two types of oral story: (1) a repeatedly reproduced narrative (a story about the war) and (2) an unprepared segment of a speech (a story about life in Irkutsk during the existence of the USSR and after its collapse) is considered in the article. The first variety in the scientific literature was called the “record” story. In the course of comparing the two fragments related to the mentioned types of narration, the phonetic, lexical and grammatical means used by the subject of speech and reflecting the specifics of the story-“record” on the theme of war are characterized. Thanks to an integrated approach to the linguistic features of the narrative, detailed conclusions are drawn regarding its organization. It has been established that at different linguistic levels the story-“record” has certain distinctive features, the most important of which are the use of functionally loaded prosodic means and the almost complete absence of speech failures, the use of a large number of bookish lexical elements, as well as grammatical structures characteristic of the official business language, written speeches. It is proved that all the identified features allow the speaker to give the features of a collectively significant memory to personal impressions of the war

Impact of IgG Fc-fragments on experimental glomerulonephritis induced by <i>Streptococcus pyogenes</i> strain binding various immunoglobulin classes

The pathogenesis of poststreptococcal glomerulonephritis (PSGN), a major complication of acute infections caused by group A streptococci (GAS) remains unclear. Several theories, based on the role of certain streptococcal virulence factors, as well as immunological mimicry between GAS and renal tissue, have been proposed. Earlier, we reported that many virulent clinical GAS isolates showing confirmed nephritogenic activity were capable of nonimmune Fc binding of monomeric or aggregated IgG. Moreover, a rabbit model of PSGN allowed to obtain findings regarding a crucial role of streptococcal IgG Fc binding proteins belonging to the M family surface proteins, in the onset of PSGN. Rabbits injected with inactivated IgGFcBP-positive streptococci, acquired changes in the renal tissue with deposited IgG and complement C3, as well as signs of immune inflammation characteristic for human PSGN. Also, it was shown that the induction of experimental glomerulonephritis could be inhibited after normal IgG or its purified Fc fragments were inoculated at early stages of the process. The data obtained in rabbits injected with group A streptococcal type M60 also showed pathogenic functions of the IgA Fc-binding proteins of GAS. The aim of the study was to examine inhibiting activity of the purified rabbit IgG Fc fragments on the manifestations of glomerulonephritis induced by S. pyogenes strains capable of binding diverse forms of immunoglobulins such native IgG, immune complexes, and IgA.Materials and methods. GAS strains of emml, emml2 and emm60 genotypes were used to induce PSGN or IgA-nephropa-thy in rabbits. Fc fragments derived from rabbit IgG were obtained by enzymatic digestion and purified by affinity chromatography on a protein G-sepharose FF column. Immunomorphological changes of renal tissue were estimated by morphometric analysis.Results. In the present study, using the rabbit model, we revealed pathological changes of different intensity and localization in the renal tissue. For streptococci of the emm1 and emm12 genotypes, PSGN was characterized by deposition of IgG or IgG-anti-IgG immune complexes within the basal glomerular membrane. Morphological changes were evaluated as a membranous-proliferative glomerulonephritis. Meanwhile, IgA-glomerulonephritis is characterized by deposition of IgA in mesangial cells of glomeruli, leading to the mesangial-proliferative glomerulonephritis or IgA-nephropathy. Intravenously administered purified Fc fragments derived from normal rabbit IgG varied in effects on pathological processes: (i) IgG Fc fragments of fully inhibited development of the PSGN induced by IgG Fc binding strain of emml genotype, (ii) IgG Fc fragments of partially reverted changes caused by the emm12 genotype strain, which was binding only to immune complexes, and (iii) had no effects on pathological changes caused by the emm60 genotype GAS strain, which was binding only IgA.Conclusion. The data obtained point and emergence of differences in mechanisms of renal lesions development at glomerulonephritis, depending on the emm genotype of GAS strain. In addition, it also confirmed GAS-derived involvement for various IgFc-receptor proteins in the pathology. Further studies on potential prophylactic or curative effects of IgG Fc fragments in PSGN should therefore be of interest. The findings might suggest a new therapeutic approach for non-suppurative poststreptococcal diseases

A role of streptokinase in experimental post-streptococcal glomerulonephritis

Post-streptococcal glomerulonephritis (PSGN) refers to the sequela of the acute infection, caused by Streptococcus pyogenes (group A streptococcus, GAS). This pathology has been studied for a long time, and today attempts are being made to identify the products of their life activity, able to initiate an immunopathological process in kidneys. Most attention has been paid to streptokinase, the enzyme transforming blood plasminogen into plasmin, capable, together with the plasmin receptor (NAPlr), of damaging the glomerular tissue, as well as activating the complement system. The aim of the study was to consider two tasks: to study the ability of the GAS-obtained enzyme to transform plasminogen of different species into plasmin as well as to study its role in the development of PSGN in rabbits having subcutaneously implanted tissue chambers. The animals were infected by inoculating GAS cultures into the chambers. Materials and methods. GAS strains of M types 1, 12, 22 and their ska– isogenic mutants were used in the study. Purified plasminogen preparations were isolated from fresh human, rabbit or mouse plasma by using chromatographic column with Lysine Sepharose 4B. To reveal the ability of streptokinase to activate plasminogen into plasmin, its preparation at a concentration of 1 mg/ml was added to 10 ìg of purified human, rabbit or mouse plasminogen. The concentration of plasmin was defined photometrically using S-2251 (Chromogenix, USA). To reproduce PSGN, four chambers were implanted under the skin in each rabbit; after the complete wound healing animals were infected and observed for three weeks. On day 14, the animals were treated with benzylpenicillin. The kidneys from survived rabbits were subjected to immunohistology analysis. Results. During in vitro experiments, M1, M12 and M22 GAS streptokinase showed distinct functional activity on human plasminogen, transforming it into plasmin: optical density indicators at ë = 405 nm were 0.4–0.7 compared with the negative control (ОD &lt; 0.001). Streptokinase did not activate mouse plasminogen (ОD = 0.001) and exerted quite a weak effect on transformation of the rabbit plasminogen into plasmin (ОD = 0.002). In experiments on PSGN induction in rabbits, we failed to detect streptokinase involvement, because no differences between initiation of glomerulonephritis by wild strains or ska– isogenic mutants were identified. Mutant strains deficient in the gene responsible for streptokinase synthesis but retained ability to bind rabbit and human IgG, caused morphological changes in kidney tissue, specific for PSGN. In addition, a comparative analysis of PSGN “rabbit” and “mouse” models developed by the same technology, was carried out and led to opposing conclusions regarding a role of streptokinase in pathogenesis of experimental glomerulonephritis. The role of IgG Fc-binding activity of GAS in development of experimental PSGN is discussed

Epizootic situation for brucellosis in the Russian Federation (review)

The World Health Organization (WHO) considers brucellosis to be one of the most dangerous and spread zoonosis in the world. The aim of the review is to summarize the current scientific data on the brucellosis in animals, to analyze the epizootic situation in the Russian Federation, Arctic Zone included, and to define the key factors of animal protection against the infection. The epizootic situation for brucellosis in farm animals, which are carriers of the three main pathogens of  brucellosis, is an urgent epidemiological problem. Their widespread occurrence is the factor determining the world-wide distribution of pathogens in most countries that indicates for the importance of control the brucellosis on an international scale. In Russia, a high epizootic risk of the spread of the disease is observed in the regions of the Volga, Southern and North Caucasian Federal Districts, in southern Siberia and Far East as well as in the Arctic. Brucellosis has the same epizootic and epidemiological significance in the Arctic regions considering the national food preferences of the peoples of the Far North. In the Russian Arctic, epizootic foci of brucellosis in cattle and reindeer have been identified and evidence of the epidemiological significance and ecological association of B. suis with the reindeer population has been presented. Specific prophylaxis of brucellosis is based on the use of vaccines. However, the problem of reindeer vaccination has not been finally resolved

IMMUNOSUPPRESSIVE EFFECTS OF ARGININE DEIMINASE FROM STREPTOCOCCUS PYOGENES

Many pathogens use metabolic pathway of arginine for successful dissemination. Bacterial arginine deiminase hydrolyzes arginine to form one molecule of ammonia and two molecules of ATP. The activity of the enzyme contributes to the improvement of survival of pathogenic bacteria in conditions of low pH at the site of infection or in phagolysosome, as well as in anaerobic conditions, and also leads to deficiency of arginine. Metabolism of arginine plays an important role in regulating the functions of immune system cells in mammals. Arginine is a substrate of enzymes NOS and arginase. Arginine depletion, potentially contributs to immunosuppression. The review analyzed the literature data on the effect of streptococcal arginine deiminase on the metabolism of arginine eukaryotic cells, and discusses immunosuppressive action of the enzyme

Quantification of Residual Organochlorine Pesticides in Medicinal Plant Raw Materials Containing Terpenoids

An important indicator of the safety of plant raw materials and herbal medicinal products is the content of residual pesticides. Its determination is particularly difficult in aromatic plants characterised by a diverse composition of terpenoids co-extracting with organochlorine pesticides and forming numerous degradation products that interfere with the analysis.The aim of the study was to develop and validate an analytical procedure for the quantification of organochlorine pesticides in plant raw materials containing terpenoids, compliant with the requirements of the State Pharmacopoeia of the Russian Federation.Materials and methods: the study analysed samples of morphologically different raw materials from 21 plant species containing terpenoids. The analysis was carried out by GLC-MS on a 450-GC gas chromatograph coupled to a 220-MS ion-trap mass spectrometer (Varian, USA) using a FactorFour VF-5ms quartz capillary column (30 m × 0.25 mm).Results: the authors developed the analytical procedure for organochlorine pesticides in medicinal plant raw materials containing terpenoids. Its specificity was confirmed by retention times and mass spectra for all the tested analytes. The recovery of pesticides was studied on model mixtures of a plant raw material and ranged from 70.04 to 99.27%. The authors established the linearity using a calibration curve for internal standard (4,4'-dibromodiphenyl) concentrations from 1.0 to 18.1 µg/mL. The procedure was linear across the entire studied range; the correlation coefficient equalled 0.999. The trueness and precision of the analytical procedure met the acceptance criteria.Conclusions: the analytical procedure has been put into use at the Testing Centre of VILAR. From 2018 to 2020, 63 samples of 21 types of medicinal plant raw materials were analysed and found to be corresponding to the safety requirements for the organochlorine pesticide content. Residual pesticides were detected in the medicinal plant raw materials in few sporadic cases