Pub Date : 2024-07-28DOI: 10.15789/2220-7619-iot-16746
E. Goncharova, Victoria D. Bets, Yulia Makusheva, E. A. Litvinova
While pathogenic protists inhabiting the reproductive tract are well studied, the gastrointestinal (GI) tract contains a constitutive protist microbiota that is an integral part of the vertebrate microbiome. Currently, the effect of protozoan infections on the host immune system and their potential contribution to disruption of mucosal immune homeostasis are not well understood. Protists, along with bacteria and viruses, are permanent representatives of the human microbiota. The main attention of researchers is focused on studying their pathogenic role in gastrointestinal diseases. However, their role in symbiotic relationships with hosts is relatively little studied. It was previously shown that the closest human ortholog of mouse Trichomonas (Tritrichomonas spp.) is Trichomonas Dientamoeba fragilis, which can cause symptoms of inflammatory bowel disease. It is currently unclear whether Dientamoeba fragilis and other protist species such as Enteromonas spp., Entamoeba dispar are commensals, pathobionts, or pathogens of the human intestinal tract. Thus, information about the mutualistic relationships between protists, the gastrointestinal microbiota, and the immune system of mice can be used to understand host-protozoan relationships in humans. The data obtained allow us to evaluate the potential contribution of commensal protozoa in the formation of protective mechanisms of the mucous membrane of animals and humans. We have previously shown that antibiotic therapy leads to an increase in the number of Tritrichomonas spp. along with a reduction in bacteria in the gut of mice with a mutation in the Muc2 gene. A mutation in this gene leads to impaired formation of the intestinal mucosa in mice. Mice with a mutation in the Muc2 gene can be used as model to study human inflammatory bowel diseases (IBDs). In this work, we conducted a comparative study of the immunological status of Muc2–/– mice harboring Tritrichomonas spp. after antibiotic therapy for 2 weeks followed by gavage of Lactobacillus johnsonii into mice and mice without introduction of probiotic microorganisms (self-recovery). Analysis of the main populations of lymphocytes in the blood, spleen and lymph nodes showed that the introduction of Lactobacillus johnsonii after antibiotic therapy leads to a significant increase in the population of T-lymphocytes in the blood and spleen, and an increase in the number of helper T cells in the lymph nodes of Muc2–/– mice compared to mice without the addition of probiotic microorganisms.
对栖息在生殖道中的致病原生动物进行了深入研究，而胃肠道（GI）中的原生动物微生物群则是脊椎动物微生物群不可或缺的一部分。目前，人们对原生动物感染对宿主免疫系统的影响及其对破坏粘膜免疫平衡的潜在作用还不甚了解。原生动物与细菌和病毒一样，是人类微生物群的永久代表。研究人员的主要注意力集中在研究它们在胃肠道疾病中的致病作用。然而，对它们在与宿主的共生关系中的作用研究相对较少。以前的研究表明，与小鼠毛滴虫（Tritrichomonas spp.）最接近的人类直向同源物是脆弱片阿米巴毛滴虫（Trichomonas Dientamoeba fragilis），它能引起炎症性肠病的症状。目前还不清楚脆弱片阿米巴和其他原生动物物种（如肠单胞菌属、变形恩塔米巴）是人类肠道的共生菌、致病菌还是病原体。因此，有关小鼠的原生动物、胃肠道微生物群和免疫系统之间的相互关系的信息可用于了解人类宿主与原生动物之间的关系。通过获得的数据，我们可以评估共生原生动物在动物和人类粘膜保护机制形成过程中的潜在贡献。我们之前已经证明，抗生素治疗会导致三联单胞菌数量增加，同时会减少 Muc2 基因突变小鼠肠道中的细菌数量。该基因的突变会导致小鼠肠道粘膜的形成受损。Muc2基因突变的小鼠可用作研究人类炎症性肠病（IBD）的模型。在这项工作中，我们对携带三联单胞菌的 Muc2-/-小鼠在抗生素治疗 2 周后灌胃约翰逊乳杆菌与未引入益生菌的小鼠（自我恢复）的免疫状态进行了比较研究。对小鼠血液、脾脏和淋巴结中主要淋巴细胞群的分析表明，与未添加益生菌的小鼠相比，在抗生素治疗后添加约翰逊乳杆菌会导致 Muc2-/-小鼠血液和脾脏中 T 淋巴细胞群显著增加，淋巴结中辅助性 T 细胞数量增加。
{"title":"Impact of Tritrichomonas spp. on the immune system of Muc2–/– mice after antibiotic therapy","authors":"E. Goncharova, Victoria D. Bets, Yulia Makusheva, E. A. Litvinova","doi":"10.15789/2220-7619-iot-16746","DOIUrl":"https://doi.org/10.15789/2220-7619-iot-16746","url":null,"abstract":"While pathogenic protists inhabiting the reproductive tract are well studied, the gastrointestinal (GI) tract contains a constitutive protist microbiota that is an integral part of the vertebrate microbiome. Currently, the effect of protozoan infections on the host immune system and their potential contribution to disruption of mucosal immune homeostasis are not well understood. Protists, along with bacteria and viruses, are permanent representatives of the human microbiota. The main attention of researchers is focused on studying their pathogenic role in gastrointestinal diseases. However, their role in symbiotic relationships with hosts is relatively little studied. It was previously shown that the closest human ortholog of mouse Trichomonas (Tritrichomonas spp.) is Trichomonas Dientamoeba fragilis, which can cause symptoms of inflammatory bowel disease. It is currently unclear whether Dientamoeba fragilis and other protist species such as Enteromonas spp., Entamoeba dispar are commensals, pathobionts, or pathogens of the human intestinal tract. Thus, information about the mutualistic relationships between protists, the gastrointestinal microbiota, and the immune system of mice can be used to understand host-protozoan relationships in humans. The data obtained allow us to evaluate the potential contribution of commensal protozoa in the formation of protective mechanisms of the mucous membrane of animals and humans. We have previously shown that antibiotic therapy leads to an increase in the number of Tritrichomonas spp. along with a reduction in bacteria in the gut of mice with a mutation in the Muc2 gene. A mutation in this gene leads to impaired formation of the intestinal mucosa in mice. Mice with a mutation in the Muc2 gene can be used as model to study human inflammatory bowel diseases (IBDs). In this work, we conducted a comparative study of the immunological status of Muc2–/– mice harboring Tritrichomonas spp. after antibiotic therapy for 2 weeks followed by gavage of Lactobacillus johnsonii into mice and mice without introduction of probiotic microorganisms (self-recovery). Analysis of the main populations of lymphocytes in the blood, spleen and lymph nodes showed that the introduction of Lactobacillus johnsonii after antibiotic therapy leads to a significant increase in the population of T-lymphocytes in the blood and spleen, and an increase in the number of helper T cells in the lymph nodes of Muc2–/– mice compared to mice without the addition of probiotic microorganisms.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"1 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141796997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-bsa-16895
N. Kosyakova, M. V. Akulenko
Broncho-obstructive syndrome (BOS) after coronavirus infection is characterized by long-term, dry and painful cough which is hard for treatment, significantly reducing the quality of life of the patients. The goal of the study: to investigate the specific features of clinical manifestations of BOS diagnosed for the first time in patients belonging to different age groups in post-COVID-19 period and to estimate the degree of mitochondrial dysfunction by the imbalance of the enzymes of cellular energy metabolism. Materials and methods. 298 patients with BOS (age 18–78) were observed continuously for 2 years. Standard clinical, biochemical and functional examination was carried out, Saint George`s Respiratory Questionnaire (SGRQ) was used. Mitochondrial dysfunction was determined by the ratio of levels of two enzymes, lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH), in peripheral blood lymphocytes. Statistical data processing was performed in STATISTICA 10.1 program package. Results. The duration and severity of BOS manifestations increased with age, they were the most prominent in the age group older than 60 y/o. Bronchial asthma was diagnosed for the first time in 85 patients, most of them belonging to the group 18–25 y/o. In all the patients with BOS, the SGRQ coeffitient was above 50, and comorbidity was established in 82.4% of the patients. The longest duration of BOS (49.4±3.5 days) was established in the group older than 60 y/o (n = 86). LDH/SDH ratio decreased from 6 to 4.8–5.2 a.u. in all the age groups. Such changes should be taken into account in the patients from young age groups. Conclusion. The revealed low values of LDH/SDH ratio have not been shown in the available literature earlier. These values demonstrate the development of secondary mitochondrial dysfunction in post-COVID-19 period in both younger and older age groups, particularly, in patients with more severe progression of BOS. Estimation of this parameter would allow to revealthe personified characteristics for each patients, which is important for quantifying the efficacy and duration of the required antioxidant therapy.
{"title":"Broncho-obstructive syndrome and the enzymes of cellular energy metabolism after coronavirus infection","authors":"N. Kosyakova, M. V. Akulenko","doi":"10.15789/2220-7619-bsa-16895","DOIUrl":"https://doi.org/10.15789/2220-7619-bsa-16895","url":null,"abstract":"Broncho-obstructive syndrome (BOS) after coronavirus infection is characterized by long-term, dry and painful cough which is hard for treatment, significantly reducing the quality of life of the patients. The goal of the study: to investigate the specific features of clinical manifestations of BOS diagnosed for the first time in patients belonging to different age groups in post-COVID-19 period and to estimate the degree of mitochondrial dysfunction by the imbalance of the enzymes of cellular energy metabolism. Materials and methods. 298 patients with BOS (age 18–78) were observed continuously for 2 years. Standard clinical, biochemical and functional examination was carried out, Saint George`s Respiratory Questionnaire (SGRQ) was used. Mitochondrial dysfunction was determined by the ratio of levels of two enzymes, lactate dehydrogenase (LDH) and succinate dehydrogenase (SDH), in peripheral blood lymphocytes. Statistical data processing was performed in STATISTICA 10.1 program package. Results. The duration and severity of BOS manifestations increased with age, they were the most prominent in the age group older than 60 y/o. Bronchial asthma was diagnosed for the first time in 85 patients, most of them belonging to the group 18–25 y/o. In all the patients with BOS, the SGRQ coeffitient was above 50, and comorbidity was established in 82.4% of the patients. The longest duration of BOS (49.4±3.5 days) was established in the group older than 60 y/o (n = 86). LDH/SDH ratio decreased from 6 to 4.8–5.2 a.u. in all the age groups. Such changes should be taken into account in the patients from young age groups. Conclusion. The revealed low values of LDH/SDH ratio have not been shown in the available literature earlier. These values demonstrate the development of secondary mitochondrial dysfunction in post-COVID-19 period in both younger and older age groups, particularly, in patients with more severe progression of BOS. Estimation of this parameter would allow to revealthe personified characteristics for each patients, which is important for quantifying the efficacy and duration of the required antioxidant therapy.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"8 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-cao-16660
A. Rak, L. G. Rudenkо, I. Isakova-Sivak
Antigen-specific T cells are an important part of antiviral responses, and modern influenza vaccines are designed to induce this mode of immunity. Live attenuated influenza vaccine (LAIV) is a potent inducer of T-cell immunity because of its ability to cause productive infection in the upper respiratory tract. Inactivated influenza vaccines (IIV) and novel vaccine candidates can also induce virus-specific T-cells when appropriate adjuvants are used. In this case, non-structural and intrinsic antigens of the master donor viruses, particularly nucleoprotein (NP), are the main targets for the development of T-cell immunity. The most commonly used donor strains for LAIVs and IIVs worldwide were derived from viruses isolated between 1933 and 1960. In this regard, the question of conservation of epitopes immunogenic for CD8⁺ T-lymphocytes (CTL-epitopes) in donor-derived NPs, i.e., the ability of cytotoxic T cells specific to the donor’s NP to recognize modern influenza A virus nucleoproteins, is relevant. The aim of the study was to evaluate the conservation of CTL-immunogenic NP epitopes of donors traditionally used to create LAIVs and IIVs. Materials and methods. Epitope NP analysis was performed for 1614 and 1767 strains of influenza A virus subtypes H1N1 and H3N2, respectively, which circulated in 2009–2023 (data from the NCBI Influenza Virus Database). Immune Epitope Database (IEDB, www.iedb.org), NetCTL’s built-in CTL-epitope prediction algorithm and NetChop proteolysis site predictor were used. CTL-epitopes were mapped to NPs of master donor viruses A/Leningrad/134/17/57 (H2N2), A/Ann Arbor/6/60 (H2N2), A/PR/8/34 (H1N1), and A/WSN/1933 (H1N1) using the CrustalO alignment algorithm in JalView 2.8.1 Software. The immunogenicity and conservation of selected epitopes were further evaluated using IEDB T-cell Immunogenicity Predictor and Epitope Conservancy Assay, respectively. Results. The majority of immunogenic CTL-epitopes of donor viruses proved to be non-conserved, i.e., not found in NPs of circulating influenza strains. Conversely, most CTL-immunogenic NP epitopes of modern viruses are absent in donor viruses and cannot be induced by vaccination with conventional vaccines. The data obtained indicate the need to actualize NP in vaccine composition by directed mutagenesis of the donor-derived NP gene or by introduction of the gene encoding NP of circulating influenza viruses into vaccine strains.
{"title":"Comparative analysis of the conservation of nucleoprotein immunogenic T-cell epitopes of master donor viruses for live and inactivated influenza vaccines","authors":"A. Rak, L. G. Rudenkо, I. Isakova-Sivak","doi":"10.15789/2220-7619-cao-16660","DOIUrl":"https://doi.org/10.15789/2220-7619-cao-16660","url":null,"abstract":"Antigen-specific T cells are an important part of antiviral responses, and modern influenza vaccines are designed to induce this mode of immunity. Live attenuated influenza vaccine (LAIV) is a potent inducer of T-cell immunity because of its ability to cause productive infection in the upper respiratory tract. Inactivated influenza vaccines (IIV) and novel vaccine candidates can also induce virus-specific T-cells when appropriate adjuvants are used. In this case, non-structural and intrinsic antigens of the master donor viruses, particularly nucleoprotein (NP), are the main targets for the development of T-cell immunity. The most commonly used donor strains for LAIVs and IIVs worldwide were derived from viruses isolated between 1933 and 1960. In this regard, the question of conservation of epitopes immunogenic for CD8⁺ T-lymphocytes (CTL-epitopes) in donor-derived NPs, i.e., the ability of cytotoxic T cells specific to the donor’s NP to recognize modern influenza A virus nucleoproteins, is relevant. The aim of the study was to evaluate the conservation of CTL-immunogenic NP epitopes of donors traditionally used to create LAIVs and IIVs. Materials and methods. Epitope NP analysis was performed for 1614 and 1767 strains of influenza A virus subtypes H1N1 and H3N2, respectively, which circulated in 2009–2023 (data from the NCBI Influenza Virus Database). Immune Epitope Database (IEDB, www.iedb.org), NetCTL’s built-in CTL-epitope prediction algorithm and NetChop proteolysis site predictor were used. CTL-epitopes were mapped to NPs of master donor viruses A/Leningrad/134/17/57 (H2N2), A/Ann Arbor/6/60 (H2N2), A/PR/8/34 (H1N1), and A/WSN/1933 (H1N1) using the CrustalO alignment algorithm in JalView 2.8.1 Software. The immunogenicity and conservation of selected epitopes were further evaluated using IEDB T-cell Immunogenicity Predictor and Epitope Conservancy Assay, respectively. Results. The majority of immunogenic CTL-epitopes of donor viruses proved to be non-conserved, i.e., not found in NPs of circulating influenza strains. Conversely, most CTL-immunogenic NP epitopes of modern viruses are absent in donor viruses and cannot be induced by vaccination with conventional vaccines. The data obtained indicate the need to actualize NP in vaccine composition by directed mutagenesis of the donor-derived NP gene or by introduction of the gene encoding NP of circulating influenza viruses into vaccine strains.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"5 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-28DOI: 10.15789/2220-7619-mic-16641
E. V. Saidakova, L. Korolevskaya, V. V. Vlasova, N. Shmagel, K. Shmagel
Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a risk factor for immunological non-response to antiretroviral therapy. In cases of immunological non-response, HIV viral load suppression occurs without an increase in CD4⁺ T-cell counts, heightening the risk of morbidity and mortality in infected individuals. T-cell exhaustion may hinder their regeneration in immunological non-responders. This study aimed to identify markers of CD4⁺ and CD8⁺ T-cell exhaustion in HIV/HCV coinfected immunological non-responders. The study examined three clinical groups: 1) HIV/HCV coinfected immunological non-responders (CD4⁺ T-cells 350/µl blood; n = 9), 2) HIV/HCV coinfected individuals with a standard response to therapy (CD4⁺ T-cells 500/µl blood; n = 9), and 3) relatively healthy volunteers without HIV and HCV infections (n = 9). Ex vivo, the number of CD4⁺ and CD8⁺ T-cells expressing the inhibitory receptor PD-1 was determined using multi-color flow cytometry. In the 7-day in vitro experiment, cell cultures were stimulated with phytohemagglutinin. The number of dying proliferated CD4⁺ and CD8⁺ T-cells (CFSElowZombieUV+) was determined using multi-color flow cytometry. The amount of interleukin-2 in the culture supernatants was measured using an enzyme-linked immunosorbent assay. It was found that in HIV/HCV coinfected immunological non-responders, there was a higher number of CD4⁺ and CD8⁺ T-cells expressing PD-1, a phenotypic marker of exhaustion, compared to the other two groups. Furthermore, the frequency of dying dividing T-cells was higher in immunological non-responders, with an increase in CD4⁺ T-cells but not CD8⁺ T-lymphocytes. Similarly, a decrease in interleukin-2 production was found in stimulated T-cells of HIV/HCV coinfected immunological non-responders in the CD4⁺ T-cell pool, but not in CD8⁺ T-lymphocytes. Thus, in HIV/HCV coinfected immunological non-responders, CD4⁺ T-cells appear exhausted both phenotypically and functionally. While CD8⁺ T-cells express inhibitory receptors, they do not show functional impairments. It appears that the specialized therapy for HIV/HCV coinfected immunological non-responders should aim to improve CD4⁺ T-cell function.
人类免疫缺陷病毒（HIV）和丙型肝炎病毒（HCV）合并感染是导致抗逆转录病毒疗法免疫无反应的一个风险因素。在免疫无应答的情况下，HIV 病毒载量会被抑制，而 CD4⁺ T 细胞数量不会增加，从而增加了感染者发病和死亡的风险。T细胞衰竭可能会阻碍免疫无反应者T细胞的再生。本研究旨在确定HIV/HCV双重感染免疫无应答者CD4⁺和CD8⁺T细胞衰竭的标志物。研究考察了三个临床组：1）HIV/HCV 合并感染的免疫无反应者（CD4⁺ T 细胞 350/µl 血液；n = 9）；2）对治疗有标准反应的 HIV/HCV 合并感染者（CD4⁺ T 细胞 500/µl 血液；n = 9）；3）未感染 HIV 和 HCV 的相对健康的志愿者（n = 9）。体外实验中，使用多色流式细胞术测定了表达抑制性受体 PD-1 的 CD4⁺ 和 CD8⁺ T 细胞的数量。在为期 7 天的体外实验中，细胞培养物受到植物血凝素的刺激。使用多色流式细胞术测定了死亡增殖的 CD4⁺ 和 CD8⁺ T 细胞（CFSElowZombieUV+）的数量。培养上清液中的白细胞介素-2 含量采用酶联免疫吸附测定法进行测定。研究发现，与其他两组相比，HIV/HCV 合并感染的免疫无应答者中表达 PD-1 的 CD4⁺ 和 CD8⁺ T 细胞数量较多，而 PD-1 是衰竭的表型标记。此外，免疫无应答者中濒死分裂 T 细胞的频率更高，CD4⁺ T 细胞增加，但 CD8⁺ T 淋巴细胞没有增加。同样，HIV/HCV 共感染免疫无反应者的 CD4⁺ T 细胞池中，受刺激的 T 细胞中白细胞介素-2 的产生量减少，但 CD8⁺ T 淋巴细胞中的白细胞介素-2 的产生量没有减少。因此，在艾滋病毒/HCV 共同感染的免疫无反应者中，CD4⁺ T 细胞在表型和功能上都已耗竭。虽然 CD8⁺ T 细胞表达抑制性受体，但它们并没有表现出功能障碍。由此看来，针对艾滋病毒/丙型肝炎病毒双重感染免疫无反应者的专门疗法应以改善 CD4⁺ T 细胞功能为目标。
{"title":"Markers of CD4⁺ AND CD8⁺ T-cell exhaustion in hiv/hcv coinfected immunological non-responders to antiretroviral therapy","authors":"E. V. Saidakova, L. Korolevskaya, V. V. Vlasova, N. Shmagel, K. Shmagel","doi":"10.15789/2220-7619-mic-16641","DOIUrl":"https://doi.org/10.15789/2220-7619-mic-16641","url":null,"abstract":"Coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) is a risk factor for immunological non-response to antiretroviral therapy. In cases of immunological non-response, HIV viral load suppression occurs without an increase in CD4⁺ T-cell counts, heightening the risk of morbidity and mortality in infected individuals. T-cell exhaustion may hinder their regeneration in immunological non-responders. This study aimed to identify markers of CD4⁺ and CD8⁺ T-cell exhaustion in HIV/HCV coinfected immunological non-responders. The study examined three clinical groups: 1) HIV/HCV coinfected immunological non-responders (CD4⁺ T-cells 350/µl blood; n = 9), 2) HIV/HCV coinfected individuals with a standard response to therapy (CD4⁺ T-cells 500/µl blood; n = 9), and 3) relatively healthy volunteers without HIV and HCV infections (n = 9). Ex vivo, the number of CD4⁺ and CD8⁺ T-cells expressing the inhibitory receptor PD-1 was determined using multi-color flow cytometry. In the 7-day in vitro experiment, cell cultures were stimulated with phytohemagglutinin. The number of dying proliferated CD4⁺ and CD8⁺ T-cells (CFSElowZombieUV+) was determined using multi-color flow cytometry. The amount of interleukin-2 in the culture supernatants was measured using an enzyme-linked immunosorbent assay. It was found that in HIV/HCV coinfected immunological non-responders, there was a higher number of CD4⁺ and CD8⁺ T-cells expressing PD-1, a phenotypic marker of exhaustion, compared to the other two groups. Furthermore, the frequency of dying dividing T-cells was higher in immunological non-responders, with an increase in CD4⁺ T-cells but not CD8⁺ T-lymphocytes. Similarly, a decrease in interleukin-2 production was found in stimulated T-cells of HIV/HCV coinfected immunological non-responders in the CD4⁺ T-cell pool, but not in CD8⁺ T-lymphocytes. Thus, in HIV/HCV coinfected immunological non-responders, CD4⁺ T-cells appear exhausted both phenotypically and functionally. While CD8⁺ T-cells express inhibitory receptors, they do not show functional impairments. It appears that the specialized therapy for HIV/HCV coinfected immunological non-responders should aim to improve CD4⁺ T-cell function.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"4 12","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141797222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-02DOI: 10.15789/2220-7619-mag-17028
R. R. Baimova, Y. Ostankova, O. V. Blinova, N. A. Stoyanova, N. K. Tokarevich
Leptospirosis is a zoonotic disease found virtually worldwide. Microscopic Agglutination Test with live leptospira (MAT) is the reference method for the serological diagnosis of leptospirosis. MAT is based on assessing serum potential to agglutinate live reference serovar Leptospira maintained at a reference laboratory. At some laboratories having own collections of isolated and reference Leptospira strains applicable for serological diagnosis, those microorganisms are maintained for many years by repeated subculturing, that increases markedly a chance of strain cross-contamination. The lack of adequate quality control for reference strains may affect data of epidemiological studies. Control of Leptospira spp. reference strains purity and stability of their antigenic composition is very important for diagnosis of leptospirosis. The study objective was to compare the 16S rRNA gene nucleotide sequences of some Leptospira strains from the collection of the St. Petersburg Pasteur Institute to with relevant sequences uploaded to GenBank. In this study, 38 Leptospira strains were investigated. Nucleotide sequences of 36 strains were deposited in the international GenBank database, inconsistencies were revealed in two strains. The study found that the control Leptospira strains from the collection of the St. Petersburg Pasteur Institute had minimal dissimilarities from international control strains. The analysis of the resultant 16S rRNA sequences has shown the presence of point mutations, transitions, deletions and insertions, regardless of the strain species. The open leptospira pan-genome demonstrates high genomic variability in species due to the capability of leptospira for lateral gene transfer in order to adapt to changing environmental conditions. The massive acquisition and loss of genes give rise to an increased species diversity. The 16S rRNA gene is suitable for screening diagnostics; however, high level of the fragment similarity and close phylogenetic relationship between different species put bounds to its use in genotyping. The presence of point nucleotide mutations is most likely associated with the evolutionary mechanisms of leptospira, their ability to horizontal gene transfer and crossing-over, including ribosomal genes, but this assumption necessitates additional research. For specimen genotyping it is necessary to select alternative genes with high specificity and sufficient level of nucleotide divergence. The study shows a need for genetic analysis of collection strains in order to control the purity of cultures.
{"title":"Molecular and genetic characterization of LEPTOSPIRA spp. collection strains from the St. Petersburg Pasteur institute based on 16S rRNA gene sequencing data","authors":"R. R. Baimova, Y. Ostankova, O. V. Blinova, N. A. Stoyanova, N. K. Tokarevich","doi":"10.15789/2220-7619-mag-17028","DOIUrl":"https://doi.org/10.15789/2220-7619-mag-17028","url":null,"abstract":"Leptospirosis is a zoonotic disease found virtually worldwide. Microscopic Agglutination Test with live leptospira (MAT) is the reference method for the serological diagnosis of leptospirosis. MAT is based on assessing serum potential to agglutinate live reference serovar Leptospira maintained at a reference laboratory. At some laboratories having own collections of isolated and reference Leptospira strains applicable for serological diagnosis, those microorganisms are maintained for many years by repeated subculturing, that increases markedly a chance of strain cross-contamination. The lack of adequate quality control for reference strains may affect data of epidemiological studies. Control of Leptospira spp. reference strains purity and stability of their antigenic composition is very important for diagnosis of leptospirosis. The study objective was to compare the 16S rRNA gene nucleotide sequences of some Leptospira strains from the collection of the St. Petersburg Pasteur Institute to with relevant sequences uploaded to GenBank. In this study, 38 Leptospira strains were investigated. Nucleotide sequences of 36 strains were deposited in the international GenBank database, inconsistencies were revealed in two strains. The study found that the control Leptospira strains from the collection of the St. Petersburg Pasteur Institute had minimal dissimilarities from international control strains. The analysis of the resultant 16S rRNA sequences has shown the presence of point mutations, transitions, deletions and insertions, regardless of the strain species. The open leptospira pan-genome demonstrates high genomic variability in species due to the capability of leptospira for lateral gene transfer in order to adapt to changing environmental conditions. The massive acquisition and loss of genes give rise to an increased species diversity. The 16S rRNA gene is suitable for screening diagnostics; however, high level of the fragment similarity and close phylogenetic relationship between different species put bounds to its use in genotyping. The presence of point nucleotide mutations is most likely associated with the evolutionary mechanisms of leptospira, their ability to horizontal gene transfer and crossing-over, including ribosomal genes, but this assumption necessitates additional research. For specimen genotyping it is necessary to select alternative genes with high specificity and sufficient level of nucleotide divergence. The study shows a need for genetic analysis of collection strains in order to control the purity of cultures.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139809437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-02DOI: 10.15789/2220-7619-fig-15637
S. Yatsyshina, M. V. Mamoshina, M. Elkina, O. A. Polyaeva, Y. V. Mikhailova, A. Shelenkov, A. Е. Egorova, V. V. Maleev
Group A streptococcal infections dominate among invasive streptococcal infections, with the major causative agent, Streptococcus pyogenes, being quite stable in the environment and bearing a large number of chromosome encoded pathogenicity factors or transmitted by horizontal transfer through bacteriophages. Different genetic variants of S. pyogenes can have a different set of pathogenicity factors able to change during pathogen evolution and determine virulence level for specific isolate. With a short incubation period, the disease can proceed with developing invasive infection and toxic shock syndrome with unfavorable outcome within 7 days from disease onset. The purpose of this article is to increase the doctors’ alertness to early recognition and diagnosis, which directly affects adequate treatment in a timely manner and disease outcome. The data on streptococcal morbidity in Russia and worldwide, review of laboratory diagnostic methods and pathogen genetic typing are presented. The maximum number of cases of streptococcal septicemia in Russia was registered in 2022, which accounted for 69% of all cases during the 2014–2022 observation period. The article also describes two clinical cases of fulminant invasive group A streptococcal infection in children with symptoms of acute respiratory viral infections at the onset of the disease. The results of various laboratory diagnostics methods verifying the diagnosis are presented. The genetic characterization of microbial isolates was performed by deep DNA sequencing. In the biological material from patients (including autopsy in one case), S. pyogenes sequence type ST-28, serotypes emm-1.25 and emm-1.0 were identified. The increasing importance of invasive streptococcal infection for health care in Russia and other countries may be associated with a possible change in dominating S. pyogenes genetic variants. In this regard, the study on circulating S. pyogenes genotypes on an ongoing basis as part of surveillance of streptococcal infection and development of vaccine for specific prevention are required.
A 组链球菌感染在侵袭性链球菌感染中占主导地位，主要致病菌化脓性链球菌在环境中相当稳定，带有大量染色体编码的致病因子，或通过噬菌体水平转移传播。化脓性链球菌的不同基因变异体具有不同的致病因子，这些致病因子可在病原体进化过程中发生变化，并决定特定分离株的毒力水平。由于潜伏期较短，该病可在发病后 7 天内发展为侵袭性感染和中毒性休克综合征，造成不良后果。本文旨在提高医生对早期识别和诊断的警惕性，这直接影响到治疗的及时性和疾病的预后。文章介绍了俄罗斯和全球链球菌发病率数据、实验室诊断方法回顾和病原体基因分型。俄罗斯链球菌败血症病例最多的年份是2022年，占2014-2022年观察期内所有病例的69%。文章还介绍了两例儿童暴发性侵袭性A组链球菌感染的临床病例，这些儿童在发病时有急性呼吸道病毒感染的症状。介绍了各种实验室诊断方法验证诊断的结果。通过 DNA 深度测序对微生物分离物进行了基因鉴定。在患者的生物材料（包括一例尸体解剖）中，确定了化脓性链球菌序列类型 ST-28、血清型 emm-1.25 和 emm-1.0。在俄罗斯和其他国家，侵袭性链球菌感染对医疗保健的重要性与日俱增，这可能与主要的化脓性链球菌基因变异的变化有关。因此，作为链球菌感染监测和特定预防疫苗开发工作的一部分，需要对循环型化脓性链球菌基因型进行持续研究。
{"title":"Fulminant invasive group A streptococcal infection in children","authors":"S. Yatsyshina, M. V. Mamoshina, M. Elkina, O. A. Polyaeva, Y. V. Mikhailova, A. Shelenkov, A. Е. Egorova, V. V. Maleev","doi":"10.15789/2220-7619-fig-15637","DOIUrl":"https://doi.org/10.15789/2220-7619-fig-15637","url":null,"abstract":"Group A streptococcal infections dominate among invasive streptococcal infections, with the major causative agent, Streptococcus pyogenes, being quite stable in the environment and bearing a large number of chromosome encoded pathogenicity factors or transmitted by horizontal transfer through bacteriophages. Different genetic variants of S. pyogenes can have a different set of pathogenicity factors able to change during pathogen evolution and determine virulence level for specific isolate. With a short incubation period, the disease can proceed with developing invasive infection and toxic shock syndrome with unfavorable outcome within 7 days from disease onset. The purpose of this article is to increase the doctors’ alertness to early recognition and diagnosis, which directly affects adequate treatment in a timely manner and disease outcome. The data on streptococcal morbidity in Russia and worldwide, review of laboratory diagnostic methods and pathogen genetic typing are presented. The maximum number of cases of streptococcal septicemia in Russia was registered in 2022, which accounted for 69% of all cases during the 2014–2022 observation period. The article also describes two clinical cases of fulminant invasive group A streptococcal infection in children with symptoms of acute respiratory viral infections at the onset of the disease. The results of various laboratory diagnostics methods verifying the diagnosis are presented. The genetic characterization of microbial isolates was performed by deep DNA sequencing. In the biological material from patients (including autopsy in one case), S. pyogenes sequence type ST-28, serotypes emm-1.25 and emm-1.0 were identified. The increasing importance of invasive streptococcal infection for health care in Russia and other countries may be associated with a possible change in dominating S. pyogenes genetic variants. In this regard, the study on circulating S. pyogenes genotypes on an ongoing basis as part of surveillance of streptococcal infection and development of vaccine for specific prevention are required.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"48 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139809338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-02DOI: 10.15789/2220-7619-ecp-13303
L. V. Kataeva, N. F. Karpukhina, A. A. Vakarina, O. N. Kolotova, T. F. Stepanova, K. B. Stepanova
Opisthorchis felineus invasion in human causes inflammatory and dyskinetic disorders of the gastrointestinal tract accompanied by altered phenotypic characteristics in colon microbiota. The aim of research — study an impact of the Escherichia coli isolate phenotypic characteristics on Klebsiella spp. bacteria, isolated from colonic contents of patients with diagnosed opisthorchiasis as well as E. coli antagonistic activity. Materials and methods. The phenotypic properties of 54 E. coli isolates and 8 genus Klebsiella isolates obtained from colonic contents of patients with diagnosed opisthorchiasis were assessed. Identification of isolates and analysis of proteomic profiles were performed using Maldi BioTyper 3.0 software. 204 co-cultivation datasets were analyzed investigating antagonistic activity of E. coli isolates with varying properties on Klebsiella spp. E. coli and Klebsiella spp. isolates were examined by whole genome sequencing. Results. E. coli bacteria with typical phenotypic characteristics showed significantly more prominent antagonistic activity against Klebsiella spp. A significantly higher level of antagonistic activity against K. oxytoca bacteria vs K. pneumoniae strains. The proteomic bacterial strain profiles were divided into clusters depending on the level of antagonistic activity. E. coli molecular serotyping for O- and H-antigens revealed the genes of enterotoxigenic, enteroinvasive and extraintestinal pathogens in 60.0% of cases. Strains with the highest antagonistic activity index, which are carriers of the genes typical to enterotoxigenic E. coli sequence serotypes O6:H1 and O6:H5, were identified. The genome of such strains consisted of the largest number of virulence gene complexes: adhesins, invasins, toxins, bacteriocins. Multilocus sequence typing and sequence serotyping of E. coli and K. pneumoniae strains established their heterogeneity; K. oxytoca isolates were identified as ST242 and ST176. All strains were characterized by homology of antibiotic resistance markers (oqxA, oqxB, fosA) and a variety of beta-lactam resistance gene variants. Conclusion. It was found that E. coli isolates with typical phenotypic characteristics and carriers of virulence gene complexes exhibited significantly more pronounced antagonistic activity against Klebsiella spp. isolated from colonic contents of patients with diagnosed opisthorchiasis.
{"title":"ESCHERICHIA COLI phenotypic characteristics and antagonistic activity in opisthorchiasis invasion","authors":"L. V. Kataeva, N. F. Karpukhina, A. A. Vakarina, O. N. Kolotova, T. F. Stepanova, K. B. Stepanova","doi":"10.15789/2220-7619-ecp-13303","DOIUrl":"https://doi.org/10.15789/2220-7619-ecp-13303","url":null,"abstract":"Opisthorchis felineus invasion in human causes inflammatory and dyskinetic disorders of the gastrointestinal tract accompanied by altered phenotypic characteristics in colon microbiota. The aim of research — study an impact of the Escherichia coli isolate phenotypic characteristics on Klebsiella spp. bacteria, isolated from colonic contents of patients with diagnosed opisthorchiasis as well as E. coli antagonistic activity. Materials and methods. The phenotypic properties of 54 E. coli isolates and 8 genus Klebsiella isolates obtained from colonic contents of patients with diagnosed opisthorchiasis were assessed. Identification of isolates and analysis of proteomic profiles were performed using Maldi BioTyper 3.0 software. 204 co-cultivation datasets were analyzed investigating antagonistic activity of E. coli isolates with varying properties on Klebsiella spp. E. coli and Klebsiella spp. isolates were examined by whole genome sequencing. Results. E. coli bacteria with typical phenotypic characteristics showed significantly more prominent antagonistic activity against Klebsiella spp. A significantly higher level of antagonistic activity against K. oxytoca bacteria vs K. pneumoniae strains. The proteomic bacterial strain profiles were divided into clusters depending on the level of antagonistic activity. E. coli molecular serotyping for O- and H-antigens revealed the genes of enterotoxigenic, enteroinvasive and extraintestinal pathogens in 60.0% of cases. Strains with the highest antagonistic activity index, which are carriers of the genes typical to enterotoxigenic E. coli sequence serotypes O6:H1 and O6:H5, were identified. The genome of such strains consisted of the largest number of virulence gene complexes: adhesins, invasins, toxins, bacteriocins. Multilocus sequence typing and sequence serotyping of E. coli and K. pneumoniae strains established their heterogeneity; K. oxytoca isolates were identified as ST242 and ST176. All strains were characterized by homology of antibiotic resistance markers (oqxA, oqxB, fosA) and a variety of beta-lactam resistance gene variants. Conclusion. It was found that E. coli isolates with typical phenotypic characteristics and carriers of virulence gene complexes exhibited significantly more pronounced antagonistic activity against Klebsiella spp. isolated from colonic contents of patients with diagnosed opisthorchiasis.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"5 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139811279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-02DOI: 10.15789/2220-7619-cat-15453
Marina V. Nikolenko, E. M. Vaseva, Natalya V. Baryshnikova, O. I. Malishevskaya
Catalase is a heme-containing enzyme belonging to protection factors that destroys peroxide compounds. The presence of catalase activity is an important ability of microorganisms that allows them to be protected from unfavorable factors as well as adapt to macroorganism conditions. Catalase along with superoxide dismutase plays an important role in pathogen resistance to phagocyte oxygen-dependent bactericidal mechanisms. The aim of the study was to investigate microsymbiont catalase activity from female reproductive tract in normocenosis and candidiasis dysbiosis using the chronobiological approach. The study was conducted on clinical isolates, isolated from female reproductive tract microsymbiocenosis. The catalase activity was determined by spectrophotometry based on 24 hour-long hydrogen peroxide reduction with 3-hours interval in winter season. Dynamic hydrogen peroxide was assessed in 3–5 experiment replicates. In some Lactobacillus spp., catalase was found containing no heme group — pseudocatalase. Chronobiological approach allowed to reveal enzyme activity from all microsymbionts. The dominant and associative microbiota isolated from healthy females was characterized by circadian (24 hours) rhythms of catalase activity early in the morning — 5 a.m. (р 0.05). Hydrogen peroxide decomposes spontaneously or via non-enzymatic catalysts, and microorganisms cope with this situation under such conditions. In microsymbionts characteristic of female reproductive tract dysbiosis, and usually found in large numbers along with decreased Lactobacillus spp. ultradian rhythms with 12- and 8-hour harmonics of catalase activity with acrophase were recorded in the morning (8 a.m.) and evening hours (8 p.m.). The minimum values of enzyme production in all cultures were recorded at 12 p.m. and 5 p.m. Therefore, the contribution of the rhythm of the studied parameter at varying degree of vaginal sterility reflects the adaptive pathogen capabilities to the conditions of existence and can be the basis for studying related regulatory mechanisms. Mesor and amplitude phase stability are universal rhythmometric parameters used to evaluate patient’s condition independent of species assignment.
{"title":"Chronobiological approach to study microsymbiont catalase activity in female reproductive tract","authors":"Marina V. Nikolenko, E. M. Vaseva, Natalya V. Baryshnikova, O. I. Malishevskaya","doi":"10.15789/2220-7619-cat-15453","DOIUrl":"https://doi.org/10.15789/2220-7619-cat-15453","url":null,"abstract":"Catalase is a heme-containing enzyme belonging to protection factors that destroys peroxide compounds. The presence of catalase activity is an important ability of microorganisms that allows them to be protected from unfavorable factors as well as adapt to macroorganism conditions. Catalase along with superoxide dismutase plays an important role in pathogen resistance to phagocyte oxygen-dependent bactericidal mechanisms. The aim of the study was to investigate microsymbiont catalase activity from female reproductive tract in normocenosis and candidiasis dysbiosis using the chronobiological approach. The study was conducted on clinical isolates, isolated from female reproductive tract microsymbiocenosis. The catalase activity was determined by spectrophotometry based on 24 hour-long hydrogen peroxide reduction with 3-hours interval in winter season. Dynamic hydrogen peroxide was assessed in 3–5 experiment replicates. In some Lactobacillus spp., catalase was found containing no heme group — pseudocatalase. Chronobiological approach allowed to reveal enzyme activity from all microsymbionts. The dominant and associative microbiota isolated from healthy females was characterized by circadian (24 hours) rhythms of catalase activity early in the morning — 5 a.m. (р 0.05). Hydrogen peroxide decomposes spontaneously or via non-enzymatic catalysts, and microorganisms cope with this situation under such conditions. In microsymbionts characteristic of female reproductive tract dysbiosis, and usually found in large numbers along with decreased Lactobacillus spp. ultradian rhythms with 12- and 8-hour harmonics of catalase activity with acrophase were recorded in the morning (8 a.m.) and evening hours (8 p.m.). The minimum values of enzyme production in all cultures were recorded at 12 p.m. and 5 p.m. Therefore, the contribution of the rhythm of the studied parameter at varying degree of vaginal sterility reflects the adaptive pathogen capabilities to the conditions of existence and can be the basis for studying related regulatory mechanisms. Mesor and amplitude phase stability are universal rhythmometric parameters used to evaluate patient’s condition independent of species assignment.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"46 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139811569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-02DOI: 10.15789/2220-7619-tio-17537
E. Krieger, O. Samodova, O. A. Svitich, R. Samoilikov, E. Meremianina, L. V. Ivanova, N. A. Bebyakova, E. N. Ilina, A. V. Pavlenko, Yu. I. Esin, A. L. Arkhipova, S. N. Kovalchuk, A. V. Kudryavtsev
Single nucleotide substitutions in gene sequence associated with conformational changes in protein receptor or in expression of interferon receptors may explain variations in human susceptibility to infection and severity of COVID-19 along with other well-known risk factors. The study aimed to investigate associations between polymorphic variants of interferon receptor genes, COVID-19 severity and prevalence of antibiotic resistance genes in the gut microbiota. Materials and methods. The study was conducted using a random sample of Arkhangelsk population aged 42 to 76 years (n = 305). The research involved gathering COVID-19 data from the Federal Register, conducting blood tests for SARS-CoV-2 antibodies and polymorphic interferon receptor gene variants, and identifying antibiotic resistance genes in stool samples. Results. During the first 12–15 months of the COVID-19 pandemic, 17.4% of the study participants had symptomatic COVID-19, while 32.8% were asymptomatic. By the Autumn of 2022, symptomatic COVID-19 cases rose up to 36.4%, while asymptomatic cases increased to 61.3%. We reveal an association between the CC genotype of the IFNAR1 gene rs2257167 variant, the presence of the T allele of IFNAR2 gene rs2229207 variant, the CCTT haplotype and symptomatic COVID-19. The GCTC haplotype was associated with pneumonia and COVID-19 severity. In November 2022, macrolide resistance genes were observed in 98.4% of cases, whereas those to beta-lactams and glycopeptides — in 26.9% and 13.8% cases, respectively. Resistance to three classes of antibiotics was observed in 4.9% and was more frequently detected in individuals with the ССТТ haplotype. Genes encoding beta-lactamases were more often found in individuals with the GCTC haplotype, those who had COVID-19 with pneumonia and those who received hospital treatment. Glycopeptide resistance genes were associated with the CC genotype of the rs2257167 variant of IFNAR1 gene. Conclusion. We identified genetic determinants of susceptibility, symptomatic infection and COVID-19 severity. The associations between polymorphic variants of interferon receptor genes and COVID-19 severity can be used to identify people with a genetic predisposition to severe infection and to determine priority groups for vaccination, including the prevention of antibiotic resistance in complicated course of viral infections.
{"title":"The impact of polymorphic variants of interferon receptor genes on COVID-19 severity and antibiotic resistance","authors":"E. Krieger, O. Samodova, O. A. Svitich, R. Samoilikov, E. Meremianina, L. V. Ivanova, N. A. Bebyakova, E. N. Ilina, A. V. Pavlenko, Yu. I. Esin, A. L. Arkhipova, S. N. Kovalchuk, A. V. Kudryavtsev","doi":"10.15789/2220-7619-tio-17537","DOIUrl":"https://doi.org/10.15789/2220-7619-tio-17537","url":null,"abstract":"Single nucleotide substitutions in gene sequence associated with conformational changes in protein receptor or in expression of interferon receptors may explain variations in human susceptibility to infection and severity of COVID-19 along with other well-known risk factors. The study aimed to investigate associations between polymorphic variants of interferon receptor genes, COVID-19 severity and prevalence of antibiotic resistance genes in the gut microbiota. Materials and methods. The study was conducted using a random sample of Arkhangelsk population aged 42 to 76 years (n = 305). The research involved gathering COVID-19 data from the Federal Register, conducting blood tests for SARS-CoV-2 antibodies and polymorphic interferon receptor gene variants, and identifying antibiotic resistance genes in stool samples. Results. During the first 12–15 months of the COVID-19 pandemic, 17.4% of the study participants had symptomatic COVID-19, while 32.8% were asymptomatic. By the Autumn of 2022, symptomatic COVID-19 cases rose up to 36.4%, while asymptomatic cases increased to 61.3%. We reveal an association between the CC genotype of the IFNAR1 gene rs2257167 variant, the presence of the T allele of IFNAR2 gene rs2229207 variant, the CCTT haplotype and symptomatic COVID-19. The GCTC haplotype was associated with pneumonia and COVID-19 severity. In November 2022, macrolide resistance genes were observed in 98.4% of cases, whereas those to beta-lactams and glycopeptides — in 26.9% and 13.8% cases, respectively. Resistance to three classes of antibiotics was observed in 4.9% and was more frequently detected in individuals with the ССТТ haplotype. Genes encoding beta-lactamases were more often found in individuals with the GCTC haplotype, those who had COVID-19 with pneumonia and those who received hospital treatment. Glycopeptide resistance genes were associated with the CC genotype of the rs2257167 variant of IFNAR1 gene. Conclusion. We identified genetic determinants of susceptibility, symptomatic infection and COVID-19 severity. The associations between polymorphic variants of interferon receptor genes and COVID-19 severity can be used to identify people with a genetic predisposition to severe infection and to determine priority groups for vaccination, including the prevention of antibiotic resistance in complicated course of viral infections.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"19 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139868830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-02-02DOI: 10.15789/2220-7619-mag-17028
R. R. Baimova, Y. Ostankova, O. V. Blinova, N. A. Stoyanova, N. K. Tokarevich
Leptospirosis is a zoonotic disease found virtually worldwide. Microscopic Agglutination Test with live leptospira (MAT) is the reference method for the serological diagnosis of leptospirosis. MAT is based on assessing serum potential to agglutinate live reference serovar Leptospira maintained at a reference laboratory. At some laboratories having own collections of isolated and reference Leptospira strains applicable for serological diagnosis, those microorganisms are maintained for many years by repeated subculturing, that increases markedly a chance of strain cross-contamination. The lack of adequate quality control for reference strains may affect data of epidemiological studies. Control of Leptospira spp. reference strains purity and stability of their antigenic composition is very important for diagnosis of leptospirosis. The study objective was to compare the 16S rRNA gene nucleotide sequences of some Leptospira strains from the collection of the St. Petersburg Pasteur Institute to with relevant sequences uploaded to GenBank. In this study, 38 Leptospira strains were investigated. Nucleotide sequences of 36 strains were deposited in the international GenBank database, inconsistencies were revealed in two strains. The study found that the control Leptospira strains from the collection of the St. Petersburg Pasteur Institute had minimal dissimilarities from international control strains. The analysis of the resultant 16S rRNA sequences has shown the presence of point mutations, transitions, deletions and insertions, regardless of the strain species. The open leptospira pan-genome demonstrates high genomic variability in species due to the capability of leptospira for lateral gene transfer in order to adapt to changing environmental conditions. The massive acquisition and loss of genes give rise to an increased species diversity. The 16S rRNA gene is suitable for screening diagnostics; however, high level of the fragment similarity and close phylogenetic relationship between different species put bounds to its use in genotyping. The presence of point nucleotide mutations is most likely associated with the evolutionary mechanisms of leptospira, their ability to horizontal gene transfer and crossing-over, including ribosomal genes, but this assumption necessitates additional research. For specimen genotyping it is necessary to select alternative genes with high specificity and sufficient level of nucleotide divergence. The study shows a need for genetic analysis of collection strains in order to control the purity of cultures.
{"title":"Molecular and genetic characterization of LEPTOSPIRA spp. collection strains from the St. Petersburg Pasteur institute based on 16S rRNA gene sequencing data","authors":"R. R. Baimova, Y. Ostankova, O. V. Blinova, N. A. Stoyanova, N. K. Tokarevich","doi":"10.15789/2220-7619-mag-17028","DOIUrl":"https://doi.org/10.15789/2220-7619-mag-17028","url":null,"abstract":"Leptospirosis is a zoonotic disease found virtually worldwide. Microscopic Agglutination Test with live leptospira (MAT) is the reference method for the serological diagnosis of leptospirosis. MAT is based on assessing serum potential to agglutinate live reference serovar Leptospira maintained at a reference laboratory. At some laboratories having own collections of isolated and reference Leptospira strains applicable for serological diagnosis, those microorganisms are maintained for many years by repeated subculturing, that increases markedly a chance of strain cross-contamination. The lack of adequate quality control for reference strains may affect data of epidemiological studies. Control of Leptospira spp. reference strains purity and stability of their antigenic composition is very important for diagnosis of leptospirosis. The study objective was to compare the 16S rRNA gene nucleotide sequences of some Leptospira strains from the collection of the St. Petersburg Pasteur Institute to with relevant sequences uploaded to GenBank. In this study, 38 Leptospira strains were investigated. Nucleotide sequences of 36 strains were deposited in the international GenBank database, inconsistencies were revealed in two strains. The study found that the control Leptospira strains from the collection of the St. Petersburg Pasteur Institute had minimal dissimilarities from international control strains. The analysis of the resultant 16S rRNA sequences has shown the presence of point mutations, transitions, deletions and insertions, regardless of the strain species. The open leptospira pan-genome demonstrates high genomic variability in species due to the capability of leptospira for lateral gene transfer in order to adapt to changing environmental conditions. The massive acquisition and loss of genes give rise to an increased species diversity. The 16S rRNA gene is suitable for screening diagnostics; however, high level of the fragment similarity and close phylogenetic relationship between different species put bounds to its use in genotyping. The presence of point nucleotide mutations is most likely associated with the evolutionary mechanisms of leptospira, their ability to horizontal gene transfer and crossing-over, including ribosomal genes, but this assumption necessitates additional research. For specimen genotyping it is necessary to select alternative genes with high specificity and sufficient level of nucleotide divergence. The study shows a need for genetic analysis of collection strains in order to control the purity of cultures.","PeriodicalId":21412,"journal":{"name":"Russian Journal of Infection and Immunity","volume":"25 3","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139869261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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