Microbiology Independent Research Journal (MIR Journal)
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Проблема бактериальных осложнений при респираторных вирусных инфекциях
Get PDFEvery person in the course of lifetime is repeatedly infected by a variety of respiratory viruses that represent the risk factors for the development of bacterial complications. The most dangerous among the etiological factors of acute respiratory viral diseases is the influenza A virus. This virus is capable to cause catastrophic pandemics with high mortality mainly due to the secondary bacterial pneumonia. As it has been shown in numerous recent studies, the main mechanism of provoking bacterial infections irrespective of the type of respiratory virus is the unbalanced response of the antiviral innate immunity - excessive interferon response and uncontrolled inflammation. The probability of severe bacterial complications in the course of acute respiratory viral infections is determined by both the virulence of the virus itself and by the composition of the respiratory microbiota at the time of the viral infection, as well as by the genetic characteristics of the organism. Occurrence of severe bacterial complications is also affected by the chronic diseases that have an impact on the regulation of the innate immune response. This review summarizes the current conception of the mechanisms of development of the post viral bacterial complications as well as the possibilities of prevention of these complications.Разнообразные респираторные вирусы многократно поражают каждого человека в течение жизни и являются фактором риска развития бактериальных осложнений. Наиболее опасным среди возбудителей острых респираторных вирусных заболеваний является вирус гриппа А, способный вызывать катастрофические пандемии, высокая смертность при которых в значительной степени обусловлена вторичной бактериальной пневмонией. В многочисленных исследованиях последних лет показано, что независимо от типа респираторного вируса основным механизмом провоцирования бактериальных инфекций является несбалансированный ответ системы врожденного противовирусного иммунитета – избыточный интерфероновый ответ и неконтролируемое воспаление. Вероятность тяжелых бактериальных осложнений при острых респираторных вирусных инфекциях определяется как вирулентностью самого вируса, так и составом респираторной микробиоты в момент вирусного заражения, а также генетическими особенностями организма и наличием хронических заболеваний, влияющих на регуляцию системы врожденного иммунного ответа. В данном обзоре суммированы современные представления о механизмах развития бактериальных осложнений, следующих за вирусной инфекцией, и возможностях их предотвращения
First report of the fungus Diaporthe phaseolorum on sunflower in Russia
Get PDFFungi of the ascomycete genus Diaporthe have been identified worldwide. Typically, Diaporthe species are saprobes, endophytes, or plant pathogens. The distinction between the species of this genus has historically been based on the combination of the morphological information, cultural characteristics, and host affiliation. The correct identification of the Diaporthe species should be carried out based on a combination of molecular genetic traits. A comprehensive analysis of Diaporthe species in the Russian Federation using molecular phylogeny methods has never been accomplished. The goal of this study was the identification of the isolate Diaporthe sp. MF 16-010, extracted from stems of Helianthus annuus L. that was collected in the Krasnodar region of the Russian Federation. According to the morphology data and DNA sequence analyses of the nuclear ribosomal internal transcribed spacer (ITS) region as well as of the translation elongation factor-1α (EF-1α), and ß-tubulin genes, the isolate MF 16-010 was identified as Diaporthe phaseolorum (Cooke & Ellis) Sacc. To the best of our knowledge, this isolate represents the first report of Diaporthe phaseolorum associated with sunflower in the Russian Federation. The development of the stem lesions as a result of the artificial inoculation of MF 16-010 to sunflower proved that this isolate is pathogenic for sunflower.Fungi of the ascomycete genus Diaporthe have been identified worldwide. Typically, Diaporthe species are saprobes, endophytes, or plant pathogens. The distinction between the species of this genus has historically been based on the combination of the morphological information, cultural characteristics, and host affiliation. The correct identification of the Diaporthe species should be carried out based on a combination of molecular genetic traits. A comprehensive analysis of Diaporthe species in the Russian Federation using molecular phylogeny methods has never been accomplished. The goal of this study was the identification of the isolate Diaporthe sp. MF 16-010, extracted from stems of Helianthus annuus L. that was collected in the Krasnodar region of the Russian Federation. According to the morphology data and DNA sequence analyses of the nuclear ribosomal internal transcribed spacer (ITS) region as well as of the translation elongation factor-1α (EF-1α), and ß-tubulin genes, the isolate MF 16-010 was identified as Diaporthe phaseolorum (Cooke & Ellis) Sacc. To the best of our knowledge, this isolate represents the first report of Diaporthe phaseolorum associated with sunflower in the Russian Federation. The development of the stem lesions as a result of the artificial inoculation of MF 16-010 to sunflower proved that this isolate is pathogenic for sunflower
Drug development and open access: approaches and perspectives
Get PDFThe development of a new medicine is a process that requires enormous time and tremendous financing. It takes 10-15 years from the discovery of an active compound to the launch of its production and the start of drug marketing with the total costs of the project reaching 1.8 billion US dollars. These large time and financial costs stem from repeated testing and elimination of a large percentage of compounds over the course of screening at each stage of preclinical and clinical trials. Many investors have lost interest in financing new drug discovery projects (or pharmaceutical start-up companies) due to the high risk and extensive time required to produce a return on investments. Since all the research data are considered confidential by pharmaceutical companies and thus never shared with scientific community, different scientific groups waste significant resources repeating the same costly experiments in drug discovery. In this article, we discuss new approaches to drug discovery involving open access to the research data and alternative financing that could significantly streamline the search for new cures for human diseases.The development of a new medicine is a process that requires enormous time and tremendous financing. It takes 10-15 years from the discovery of an active compound to the launch of its production and the start of drug marketing with the total costs of the project reaching 1.8 billion US dollars. These large time and financial costs stem from repeated testing and elimination of a large percentage of compounds over the course of screening at each stage of preclinical and clinical trials. Many investors have lost interest in financing new drug discovery projects (or pharmaceutical start-up companies) due to the high risk and extensive time required to produce a return on investments. Since all the research data are considered confidential by pharmaceutical companies and thus never shared with scientific community, different scientific groups waste significant resources repeating the same costly experiments in drug discovery. In this article, we discuss new approaches to drug discovery involving open access to the research data and alternative financing that could significantly streamline the search for new cures for human diseases
Адаптация метода количественной ПЦР для выявления представителей микобиоты зерновых культур
Get PDFThe content of fungal DNA and mycotoxins in cereal crops (31 varieties of wheat, oats, and barley) was quantitatively determined and used for comparative characterization of grains. The quantitative PCR has been adapted for the analysis of the target DNA of Alternaria spp., Bipolaris sorokiniana (B. sorokiniana), Fusarium graminearum (F. graminearum), F. culmorum, and F. sporotrichioides fungi, which are often present in mycobiota of small grain cereals. The content of DNA of aggressive pathogen B. sorokiniana was determined using quantitative PCR for the first time. The DNA of Alternaria fungi was found abundantly in all grain samples, but its content in the oat was significantly higher compared to barley and wheat (5 and 9 times higher, respectively). In barley grain, the content of B. sorokiniana DNA was on average significantly higher than in the grains of oats and wheat. The presence of F. graminearum DNA was established in all the analyzed grain samples while the F. culmorum DNA was found in 70% of the oat’s samples and in all samples of barley and wheat. Mycotoxin deoxynivalenol (DON) produced by these fungi was detected in all analyzed cereal grains in a range from 77 to 4133 μg/kg. The DNA of F. sporotrichioides was detected in 70% of oats and 50% of barley samples but was not found in wheat. The T-2 toxin produced by this fungus was detected in 45% of all samples within the range from 2 to 89 μg/kg. The statistically significant positive correlation with the Pearson correlation coefficient (r) equal to 0.49 (p<0.05) was observed between the amount of F. graminearum DNA and DON in the grain samples. Another significant positive correlation (r = 0.72, p<0.01) was found between DNA contents of Alternaria fungi and F. sporotrichioides in the grain samples. This leads to the suggestion that conditions for growth of these fungi in grain substrates are similar.Проведена сравнительная оценка содержания ДНК грибов и микотоксинов в зерне 31 сорта пшеницы, овса и ячменя. Метод количественной ПЦР был адаптирован для выявления ДНК грибов, часто встречающихся в микобиоте зерновых культур: Alternaria spp., Bipolaris sorokiniana (B. sorokiniana), Fusarium graminearum (F. graminearum), F. culmorum и F. sporotrichioides. Количественное выявление в зерне ДНК гриба B. sorokiniana проведено впервые. ДНК грибов Alternaria выявлена во всех образцах в диапазоне от 184×10-4 до 11160×10-4 пг/нг общей ДНК, но в зерне овса, по сравнению с зерном ячменя и пшеницы, ее количества были больше в 5 и 9 раз соответственно. ДНК B. sorokiniana выявлена во всех образцах зерна ячменя и овса, а также в 56% образцов пшеницы. В зерне ячменя содержание ДНК B. Sorokiniana в среднем было существенно выше (402×10-4 пг/нг), чем в зерне овса (51×10-4 пг/нг) и пшеницы (10×10-4 пг/нг). Присутствие ДНК гриба F. graminearum установлено в зерне всех анализированных образцов в диапазоне от 14×10-4 до 1110×10-4 пг/нг, ДНК F. culmorum выявлена в 70% образцов овса и в 100% образцов ячменя и пшеницы в количестве от 8×10-4 до 90×10-4 пг/нг. Микотоксин дезоксиниваленол (ДОН), продуцируемый грибами F. graminearum и F. culmorum, выявлен в зерне всех образцов в диапазоне от 77 до 4133 мкг/кг. ДНК F. sporotrichioides, продуцирующего Т-2 токсин, обнаружена в 70% образцов овса и 50% образцов ячменя в количестве от 5×10-4 до 47×10-4 пг/нг и не выявлена в зерне пшеницы. Количество T-2 токсина, обнаруженного в 45% образцов, не превышало 89 мкг/кг. Установлена достоверная положительная связь между количествами ДНК F. graminearum и ДОН в зерне. Коэффициент корреляции Пирсона (r) составил 0.49 (p <0.05). Также выявлена положительная связь (r = 0.72, p <0.01) между количествами ДНК Alternaria spp. и F. sporotrichioides, что предполагает сходство условий для развития этих грибов на зерновом субстрате
Live poultry vaccines against highly pathogenic avian influenza viruses
Get PDFThe widespread circulation of highly pathogenic avian influenza viruses (HPAIVs) and their occasional transmission to humans creates a constant pandemic threat and leads to significant economic losses in the poultry industry. The development of an effective and safe vaccine for the broad protection of poultry from H5N1 HPAIVs remains an important goal. Prevention of the virus transmission between ducks and chickens is important for the efficient control of the spread of avian influenza. The oral administration of live vaccines corresponds to the natural route of infection that leads to virus replication in the intestinal epithelial cells that cause a well-balanced and broad immune response providing protection against the viruses of distant clades. The broad protection is the important advantage of live-attenuated influenza vaccines when compared to inactivated ones. Here, we give an overview of the latest approaches and results in the development of live poultry vaccine candidates against HPAIVs.The widespread circulation of highly pathogenic avian influenza viruses (HPAIVs) and their occasional transmission to humans creates a constant pandemic threat and leads to significant economic losses in the poultry industry. The development of an effective and safe vaccine for the broad protection of poultry from H5N1 HPAIVs remains an important goal. Prevention of the virus transmission between ducks and chickens is important for the efficient control of the spread of avian influenza. The oral administration of live vaccines corresponds to the natural route of infection that leads to virus replication in the intestinal epithelial cells that cause a well-balanced and broad immune response providing protection against the viruses of distant clades. The broad protection is the important advantage of live-attenuated influenza vaccines when compared to inactivated ones. Here, we give an overview of the latest approaches and results in the development of live poultry vaccine candidates against HPAIVs
Adaptation of the quantitative PCR method for the detection of the main representatives of cereal grain mycobiota
Get PDFThe content of fungal DNA and mycotoxins in cereal crops (31 varieties of wheat, oats, and barley) was quantitatively determined and used for comparative characterization of grains. The quantitative PCR has been adapted for the analysis of the target DNA of Alternaria spp., Bipolaris sorokiniana (B. sorokiniana), Fusarium graminearum (F. graminearum), F. culmorum, and F. sporotrichioides fungi, which are often present in mycobiota of small grain cereals. The content of DNA of aggressive pathogen B. sorokiniana was determined using quantitative PCR for the first time. The DNA of Alternaria fungi was found abundantly in all grain samples, but its content in the oat was significantly higher compared to barley and wheat (5 and 9 times higher, respectively). In barley grain, the content of B. sorokiniana DNA was on average significantly higher than in the grains of oats and wheat. The presence of F. graminearum DNA was established in all the analyzed grain samples while the F. culmorum DNA was found in 70% of the oat’s samples and in all samples of barley and wheat. Mycotoxin deoxynivalenol (DON) produced by these fungi was detected in all analyzed cereal grains in a range from 77 to 4133 μg/kg. The DNA of F. sporotrichioides was detected in 70% of oats and 50% of barley samples but was not found in wheat. The T-2 toxin produced by this fungus was detected in 45% of all samples within the range from 2 to 89 μg/kg. The statistically significant positive correlation with the Pearson correlation coefficient (r) equal to 0.49 (p<0.05) was observed between the amount of F. graminearum DNA and DON in the grain samples. Another significant positive correlation (r = 0.72, p<0.01) was found between DNA contents of Alternaria fungi and F. sporotrichioides in the grain samples. This leads to the suggestion that conditions for growth of these fungi in grain substrates are similar.The content of fungal DNA and mycotoxins in cereal crops (31 varieties of wheat, oats, and barley) was quantitatively determined and used for comparative characterization of grains. The quantitative PCR has been adapted for the analysis of the target DNA of Alternaria spp., Bipolaris sorokiniana (B. sorokiniana), Fusarium graminearum (F. graminearum), F. culmorum, and F. sporotrichioides fungi, which are often present in mycobiota of small grain cereals. The content of DNA of aggressive pathogen B. sorokiniana was determined using quantitative PCR for the first time. The DNA of Alternaria fungi was found abundantly in all grain samples, but its content in the oat was significantly higher compared to barley and wheat (5 and 9 times higher, respectively). In barley grain, the content of B. sorokiniana DNA was on average significantly higher than in the grains of oats and wheat. The presence of F. graminearum DNA was established in all the analyzed grain samples while the F. culmorum DNA was found in 70% of the oat’s samples and in all samples of barley and wheat. Mycotoxin deoxynivalenol (DON) produced by these fungi was detected in all analyzed cereal grains in a range from 77 to 4133 μg/kg. The DNA of F. sporotrichioides was detected in 70% of oats and 50% of barley samples but was not found in wheat. The T-2 toxin produced by this fungus was detected in 45% of all samples within the range from 2 to 89 μg/kg. The statistically significant positive correlation with the Pearson correlation coefficient (r) equal to 0.49 (p<0.05) was observed between the amount of F. graminearum DNA and DON in the grain samples. Another significant positive correlation (r = 0.72, p<0.01) was found between DNA contents of Alternaria fungi and F. sporotrichioides in the grain samples. This leads to the suggestion that conditions for growth of these fungi in grain substrates are similar
Enhancement of the immunogenicity of influenza A virus by the inhibition of immunosuppressive function of NS1 protein
Get PDFThe truncation of the nonstructural NS1 protein is a novel approach for the generation of immunogenic attenuated influenza viruses. However, the innate immune mechanisms that cause the increased immunogenicity of influenza viruses with altered NS1 proteins are poorly understood. The goal of this study was to compare the immune responses in mice immunized with two variants of the influenza A/Puerto Rico/8/1934 (A/PR8) virus: the wild type virus (А/PR8/full NS) and the variant with the NS1 protein shortened to 124 amino acid residues (А/PR8/NS124). The investigated parameters of immunity included cytokine production, the dynamic variation of the innate immune cell populations, and the rate of the influenza-specific T-cell responses. An intraperitoneal route of immunization was chosen due to the variability in the replication capacity of the investigated viruses in the respiratory tract. The levels of interferon β (IFNβ), tumor necrosis factor α (TNFα), monocyte chemo-attractant protein 1 (MCP1), interleukin 6 (IL6), and IL27 in peritoneal washings of mice immunized with А/PR8/NS124 were significantly higher compared to the mice immunized with the wild-type virus. The А/PR8/NS124 treated group showed a delayed attraction of monocytes and neutrophils as well as a more pronounced reduction in the percentage of dendritic cells in the peritoneal cavity. The expression level of the CD86 activation marker on the cells expressing the molecules of the major histocompatibility complex II (MHCII+) was significantly higher in mice immunized with А/PR8/NS124 than in the group immunized with А/PR8/full NS. Finally, immunization with А/PR8/NS124 led to an increased formation of influenza-specific CD8+ effector T-cells characterized by the simultaneous production of IFNγ, IL2, and TNFα. We hypothesize that elevated cytokine production, enhanced dendritic cell migration, and increased CD86 expression on antigen-presenting cells upon immunization with А/PR8/NS124 lead to a more effective presentation of viral antigens and, therefore, promote an increased antigen-specific CD8+ immune response.The truncation of the nonstructural NS1 protein is a novel approach for the generation of immunogenic attenuated influenza viruses. However, the innate immune mechanisms that cause the increased immunogenicity of influenza viruses with altered NS1 proteins are poorly understood. The goal of this study was to compare the immune responses in mice immunized with two variants of the influenza A/Puerto Rico/8/1934 (A/PR8) virus: the wild type virus (А/PR8/full NS) and the variant with the NS1 protein shortened to 124 amino acid residues (А/PR8/NS124). The investigated parameters of immunity included cytokine production, the dynamic variation of the innate immune cell populations, and the rate of the influenza-specific T-cell responses. An intraperitoneal route of immunization was chosen due to the variability in the replication capacity of the investigated viruses in the respiratory tract. The levels of interferon β (IFNβ), tumor necrosis factor α (TNFα), monocyte chemo-attractant protein 1 (MCP1), interleukin 6 (IL6), and IL27 in peritoneal washings of mice immunized with А/PR8/NS124 were significantly higher compared to the mice immunized with the wild-type virus. The А/PR8/NS124 treated group showed a delayed attraction of monocytes and neutrophils as well as a more pronounced reduction in the percentage of dendritic cells in the peritoneal cavity. The expression level of the CD86 activation marker on the cells expressing the molecules of the major histocompatibility complex II (MHCII+) was significantly higher in mice immunized with А/PR8/NS124 than in the group immunized with А/PR8/full NS. Finally, immunization with А/PR8/NS124 led to an increased formation of influenza-specific CD8+ effector T-cells characterized by the simultaneous production of IFNγ, IL2, and TNFα. We hypothesize that elevated cytokine production, enhanced dendritic cell migration, and increased CD86 expression on antigen-presenting cells upon immunization with А/PR8/NS124 lead to a more effective presentation of viral antigens and, therefore, promote an increased antigen-specific CD8+ immune response
Первая находка гриба Diaporthe phaseolorum на подсолнечнике в России
Get PDFFungi of the ascomycete genus Diaporthe have been identified worldwide. Typically, Diaporthe species are saprobes, endophytes, or plant pathogens. The distinction between the species of this genus has historically been based on the combination of the morphological information, cultural characteristics, and host affiliation. The correct identification of the Diaporthe species should be carried out based on a combination of molecular genetic traits. A comprehensive analysis of Diaporthe species in the Russian Federation using molecular phylogeny methods has never been accomplished. The goal of this study was the identification of the isolate Diaporthe sp. MF 16-010, extracted from stems of Helianthus annuus L. that was collected in the Krasnodar region of the Russian Federation. According to the morphology data and DNA sequence analyses of the nuclear ribosomal internal transcribed spacer (ITS) region as well as of the translation elongation factor-1α (EF-1α), and ß-tubulin genes, the isolate MF 16-010 was identified as Diaporthe phaseolorum (Cooke & Ellis) Sacc. To the best of our knowledge, this isolate represents the first report of Diaporthe phaseolorum associated with sunflower in the Russian Federation. The development of the stem lesions as a result of the artificial inoculation of MF 16-010 to sunflower proved that this isolate is pathogenic for sunflower.Грибы рода Diaporthe широко распространены по всему миру, многие виды являются патогенами экономически значимых культур, в том числе и подсолнечника. Традиционно идентификацию видов Diaporthe осуществляли по морфологическим, морфолого-культуральным признакам и связи с питающим растением. Достоверную идентификацию до уровня вида представителей этого рода на настоящий момент рекомендуется осуществлять, основываясь на изучении молекулярно-генетических признаков. Комплексное изучение видов Diaporthe в России с применением методов молекулярной филогении не проводилось. Представленная работа посвящена идентификации изолята Diaporthe sp., выделенного из подсолнечника, собранного в Краснодарском крае. Согласно полученным результатам изучения молекулярно-генетических (нуклеотидные последовательности области внутренних транскрибируемых спейсеров рибосомальной ДНК, генов β-тубулина и фактора элонгации трансляции-1α) и морфологических признаков, изолят MF 16-010 был идентифицирован как вид Diaporthe phaseolorum (Cooke & Ellis) Sacc. На территории России этот изолят является первой достоверной находкой данного вида на подсолнечнике. В результате искусственной инокуляции было показано, что изолят MF 16-010 является для подсолнечника патогенным
Усиление иммуногенности вируса гриппа A путем подавления иммуносупрессорной функции белка NS1
Get PDFThe truncation of the nonstructural NS1 protein is a novel approach for the generation of immunogenic attenuated influenza viruses. However, the innate immune mechanisms that cause the increased immunogenicity of influenza viruses with altered NS1 proteins are poorly understood. The goal of this study was to compare the immune responses in mice immunized with two variants of the influenza A/Puerto Rico/8/1934 (A/PR8) virus: the wild type virus (А/PR8/full NS) and the variant with the NS1 protein shortened to 124 amino acid residues (А/PR8/NS124). The investigated parameters of immunity included cytokine production, the dynamic variation of the innate immune cell populations, and the rate of the influenza-specific T-cell responses. An intraperitoneal route of immunization was chosen due to the variability in the replication capacity of the investigated viruses in the respiratory tract. The levels of interferon β (IFNβ), tumor necrosis factor α (TNFα), monocyte chemo-attractant protein 1 (MCP1), interleukin 6 (IL6), and IL27 in peritoneal washings of mice immunized with А/PR8/NS124 were significantly higher compared to the mice immunized with the wild-type virus. The А/PR8/NS124 treated group showed a delayed attraction of monocytes and neutrophils as well as a more pronounced reduction in the percentage of dendritic cells in the peritoneal cavity. The expression level of the CD86 activation marker on the cells expressing the molecules of the major histocompatibility complex II (MHCII+) was significantly higher in mice immunized with А/PR8/NS124 than in the group immunized with А/PR8/full NS. Finally, immunization with А/PR8/ NS124 led to an increased formation of influenza-specific CD8+ effector T-cells characterized by the simultaneous production of IFNγ, IL2, and TNFα. We hypothesize that elevated cytokine production, enhanced dendritic cell migration, and increased CD86 expression on antigen-presenting cells upon immunization with А/PR8/NS124 lead to a more effective presentation of viral antigens and, therefore, promote an increased antigen-specific CD8+ immune response.Укорочение неструктурного белка NS1 является перспективным методом создания аттенуированных высокоиммуногенных вирусов гриппа. Однако механизмы врожденного иммунитета, обуславливающие повышенную иммуногенность штаммов с модифицированным NS1 в настоящее время изучены недостаточно. Целью данной работы было сравнение продукции цитокинов, динамики изменения популяционного состава клеток врожденного иммунитета и уровня адаптивного Т-клеточного иммунного ответа после иммунизации мышей двумя вариантами вируса гриппа А/Puerto Rico/8/1934 (A/PR8): вирусом дикого типа А/PR8/full NS и вирусом с укороченным до 124 аминокислотных остатков белком NS1 (А/PR8/NS124). В данном исследовании для компенсации различий в репродуктивной активности исследуемых штаммов в респираторном тракте был выбран интраперитонеальный способ введения вирусов. Уровень интерферона β (IFNβ), фактора некроза опухолей α (TNFα), моноцитарного хемоаттрактантного белка 1 (MCP1), интерлейкина 6 (IL6) и IL27 в перитонеальных смывах мышей, иммунизированных А/PR8/NS124, был существенно выше, чем в группе, получившей А/PR8/ full NS. В то же время группа А/PR8/NS124 характеризовалась замедленным привлечением моноцитов и нейтрофилов в перитонеальную полость и более выраженным снижением относительного содержания дендритных клеток по сравнению с А/PR8/full NS. Важно, что уровень экспрессии активационного маркера CD86 на клетках, экспрессирующих молекулы главного комплекса гистосовместимости II (MHCII+) перитонеальной полости мышей, иммунизированных штаммом А/PR8/NS124, имел более высокие значения по сравнению с группой А/PR8/full NS. Анализ адаптивного иммунного ответа показал, что иммунизация штаммом А/PR8/NS124 приводит к формированию повышенного содержания вирус-специфических CD8+-эффекторных Т-лимфоцитов, характеризующихся одновременной продукцией IFNγ, IL2 и TNFα. Мы предполагаем, что повышенная продукция цитокинов, усиленная миграция дендритных клеток, а также сохранение высокого уровня экспрессии CD86 на антигенпрезентирующих клетках (АПК) мышей через 24 ч после иммунизации штаммом А/PR8/NS124 приводит к более эффективной презентации антигенов вируса гриппа и, как следствие, к усилению вирусспецифического Т-клеточного иммунного ответа
Fighting bacterial resistance: approaches, challenges, and opportunities in the search for new antibiotics. Part 1. Antibiotics used in clinical practice: mechanisms of action and the development of bacterial resistance
Get PDFHundreds of thousands of people are dying every year in the world from infections caused by drug resistant bacteria. Antibiotic resistance is a rapidly increasing problem mostly as a result of the worldwide overuse and misuse of antibiotics for conditions that do not require them. The rapid spread of antibiotic resistance in bacteria makes it necessary to intensify the development of new antibiotics and new methods to combat drug resistant bacteria. The goal of this publication is to review the approaches to finding new antibiotics that are active against drug resistant bacteria. The first part of this review is focused on an analysis of the mechanisms of action of antibiotics that are used in clinical practice as well as the mechanisms of bacterial resistance. The molecular structure and modes of action of these antibiotics are reviewed with examples of detailed mechanisms of drugs interaction with the targets in bacteria. General and specific mechanisms of bacterial resistance to these antibiotics are described. Examples of new antibiotics development active against the drug resistant bacteria are presented.Hundreds of thousands of people are dying every year in the world from infections caused by drug resistant bacteria. Antibiotic resistance is a rapidly increasing problem mostly as a result of the worldwide overuse and misuse of antibiotics for conditions that do not require them. The rapid spread of antibiotic resistance in bacteria makes it necessary to intensify the development of new antibiotics and new methods to combat drug resistant bacteria. The goal of this publication is to review the approaches to finding new antibiotics that are active against drug resistant bacteria. The first part of this review is focused on an analysis of the mechanisms of action of antibiotics that are used in clinical practice as well as the mechanisms of bacterial resistance. The molecular structure and modes of action of these antibiotics are reviewed with examples of detailed mechanisms of drugs interaction with the targets in bacteria. General and specific mechanisms of bacterial resistance to these antibiotics are described. Examples of new antibiotics development active against the drug resistant bacteria are presented