Andrey Anisimov - Academia.edu (original) (raw)
Papers by Andrey Anisimov
The rough-type lipopolysaccharide (LPS) of the plague pathogen, Yersinia pestis, was studied afte... more The rough-type lipopolysaccharide (LPS) of the plague pathogen, Yersinia pestis, was studied after mild-acid and strong-alkaline degradations by chemical analyses, NMR spectroscopy and electrospray-ionization mass spectrometry, and the following structure of the core region was determined: where L-aD -Hep stands for L-glycero-aD -manno-heptose, Sug1 for either 3-deoxy-aD -manno-oct-2-ulosonic acid (a-Kdo) or D-glycero-aD -talo-oct-2-ulosonic acid (a-Ko), and Sug2 for either b-D-galactose or D-glycero-aD -manno-heptose. A minority of the LPS molecules lacks GlcNAc.
Russian Journal of Infection and Immunity
Genomic, transcriptome or (and) proteomic comparison of closely related virulent and avirulent mi... more Genomic, transcriptome or (and) proteomic comparison of closely related virulent and avirulent microbial strains underlies the search for new pathogenicity factors, potential molecular targets for etiotropic therapy, vaccine prevention and immunotherapy of infectious diseases. This investigation was aimed in testing the ability of method of testicular animalization to select phylogenetically close pairs of Y. pestis strains, which dramatically differ in their pathogenicity for guinea pigs, from the populations of as a rule subcutaneously avirulent for guinea pigs “vole” strains of the plague pathogen. Animalization of Y. pestis cultures were performed on guinea pig males by fourfold testicular passage with reducing infective dose. There was no correlation between the ability to cause generalized infectious process (death) after testicular and subcutaneous infection of guinea pigs, but testicular passages made it possible to enrich bacterial culture with a portion of microbes display...
Immunization with the capsular FI antigen induces protection against
Biomolecules, 2021
Lipopolysaccharide (LPS), localized in the outer leaflet of the outer membrane, serves as the maj... more Lipopolysaccharide (LPS), localized in the outer leaflet of the outer membrane, serves as the major surface component of the Gram-negative bacterial cell envelope responsible for the activation of the host’s innate immune system. Variations of the LPS structure utilized by Gram-negative bacteria promote survival by providing resistance to components of the innate immune system and preventing recognition by TLR4. This review summarizes studies of the biosynthesis of Yersinia pseudotuberculosis complex LPSs, and the roles of their structural components in molecular mechanisms of yersiniae pathogenesis and immunogenesis.
Biomolecules, 2020
Despite the relatively low incidence of plague, its etiological agent, Yersinia pestis, is an exc... more Despite the relatively low incidence of plague, its etiological agent, Yersinia pestis, is an exceptional epidemic danger due to the high infectivity and mortality of this infectious disease. Reports on the isolation of drug-resistant Y. pestis strains indicate the advisability of using asymmetric responses, such as phage therapy and vaccine prophylaxis in the fight against this problem. The current relatively effective live plague vaccine is not approved for use in most countries because of its ability to cause heavy local and system reactions and even a generalized infectious process in people with a repressed immune status or metabolic disorders, as well as lethal infection in some species of nonhuman primates. Therefore, developing alternative vaccines is of high priority and importance. However, until now, work on the development of plague vaccines has mainly focused on screening for the potential immunogens. Several investigators have identified the protective potency of bacte...
Problems of Particularly Dangerous Infections, 2015
Molecular Genetics Microbiology and Virology (Russian version), 2019
Чума-зоонозная инфекция, чей возбудитель был причиной гибели сотен миллионов людей. Широкий круг ... more Чума-зоонозная инфекция, чей возбудитель был причиной гибели сотен миллионов людей. Широкий круг хозяев и переносчиков в сочетании с географической разобщенностью отдельных природных очагов чумы с различными экологическими условиями существования способствуют формированию политипического вида Y. pestis-селекции генетических вариантов, специфичных для определенных природных очагов. Усилиями мирового консорциума исследователей построена согласованная глобальная филограмма SNP-типов чумного микроба, но на просторах России не стихают споры по поводу внутривидовой таксономии Y. pestis. В работе систематики очень много специфического, индивидуального, складывающегося на основе личного опыта. Здесь важно умение следовать старому правилу, требующему, чтобы границы проводили там, где их провела природа, и не проводили там, где она их не проводила. Исходя из этого, мы предлагаем рациональный вариант приведения номенклатуры чумного микроба в соответствие с правилами Международного кодекса номенклатуры бактерий и эволюционной таксономии.
PloS one, 2016
It has been shown previously that several endemic Y. pestis isolates with limited virulence conta... more It has been shown previously that several endemic Y. pestis isolates with limited virulence contained the I259 isoform of the outer membrane protease Pla, while the epidemic highly virulent strains possessed only the T259 Pla isoform. Our sequence analysis of the pla gene from 118 Y. pestis subsp. microtus strains revealed that the I259 isoform was present exclusively in the endemic strains providing a convictive evidence of more ancestral origin of this isoform. Analysis of the effects of the I259T polymorphism on the intrinsic disorder propensity of Pla revealed that the I259T mutation slightly increases the intrinsic disorder propensity of the C-terminal tail of Pla and makes this protein slightly more prone for disorder-based protein-protein interactions, suggesting that the T259 Pla could be functionally more active than the I259 Pla. This assumption was proven experimentally by assessing the coagulase and fibrinolytic activities of the two Pla isoforms in human plasma, as well...
Advances in experimental medicine and biology, 2016
Plague still poses a significant threat to human health and as a reemerging infection is unfamili... more Plague still poses a significant threat to human health and as a reemerging infection is unfamiliar to the majority of the modern medical doctors. In this chapter, the plague is described according to Dr. Nikiforov's experiences in the diagnosis and treatment of patients, and also a review of the relevant literature on this subject is provided. The main modern methods and criteria for laboratory diagnosis of plague are briefly described. The clinical presentations include the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Early diagnosis and the prompt initiation of treatment reduce the mortality rate associated with bubonic plague and septicemic plague to 5-50 %; although a delay of more than 24 h in the administration of antibiotics and antishock treatment can be fatal for plague patients. Most human cases can successfully be treated with antibiotics.
Journal of biomolecular structure & dynamics, Jan 3, 2016
The Yersinia pestis outer membrane porin F (OmpF) is a transmembrane protein located in the outer... more The Yersinia pestis outer membrane porin F (OmpF) is a transmembrane protein located in the outer membrane of this Gram-negative bacterium which is the causative agent of plague, where it plays a significant role in controlling the selective permeability of the membrane. The amino acid sequences of OmpF proteins from 48 Y. pestis strains representing all currently available phylogenetic groups of this Gram-negative bacterium were recently deduced. Comparison of these amino acid sequences revealed that the OmpF can be present in four isoforms, the pestis-pestis type, and the pestis-microtus types I, II, and III. OmpF of the most recent pestis-pestis type has an alanine residue at the position 148, where all the pestis-microtus types have threonine there (T148A polymorphism). The variability of different pestis-microtus types is caused by an additional polymorphism at the 193rd position, where the OmpFs of the pestis-microtus type II and type III have isoleucine-glycine (IG(+)193) or ...
PloS one, 2016
Yersinia pestis Caf1 is a multifunctional protein responsible for antiphagocytic activity and is ... more Yersinia pestis Caf1 is a multifunctional protein responsible for antiphagocytic activity and is a key protective antigen. It is generally conserved between globally distributed Y. pestis strains, but Y. pestis subsp. microtus biovar caucasica strains circulating within populations of common voles in Georgia and Armenia were reported to carry a single substitution of alanine to serine. We investigated polymorphism of the Caf1 sequences among other Y. pestis subsp. microtus strains, which have a limited virulence in guinea pigs and in humans. Sequencing of caf1 genes from 119 Y. pestis strains belonging to different biovars within subsp. microtus showed that the Caf1 proteins exist in three isoforms, the global type Caf1NT1 (Ala48 Phe117), type Caf1NT2 (Ser48 Phe117) found in Transcaucasian-highland and Pre-Araks natural plague foci #4-7, and a novel Caf1NT3 type (Ala48 Val117) endemic in Dagestan-highland natural plague focus #39. Both minor types are the progenies of the global iso...
Russian Journal of Infection and Immunity, 2015
Резюме. Чума была причиной трех пандемий и привела к гибели миллионов людей. Чума-типичный зооноз... more Резюме. Чума была причиной трех пандемий и привела к гибели миллионов людей. Чума-типичный зооноз, и ее возбудитель-Yersinia pestis, циркулирует в популяциях диких грызунов, обитающих в природных очагах чумы на всех материках, кроме Австралии. Передача чумы осуществляется укусами блох. Циркуляция Y. pestis в природных очагах чумы обеспечивается целым рядом факторов патогенности. В обзоре рассматривается один из них-активатор плазминогена Pla. Этот белок является одним из представителей омптинов-семейства протеаз наружных мембран патогенных энтеробактерий, обеспечивающих колонизацию отдельных органов и даже генерализацию инфекции в результате успешного противостояния врожденному иммунитету хозяина. Описаны история открытия, генетический контроль, условия биосинтеза, выделение, очистка и физико-химические свойства активатора плазминогена. Высокоочищенные препараты активатора плазминогена утрачивают свою ферментативную активность, а ренатурация в присутствии липоолигосахарида Y. pestis восстанавливает энзиматические свойства Pla. Этот фактор патогенности отсутствует у наиболее древней филогенетической группы чумного микроба, bv. caucasica, а предшественник остальных групп Y. pestis subsp. microtus получил в результате горизонтального переноса изоформу Pla, близкую по свойствам омптинам менее вирулентных энтеробактерий. Затем в ходе микроэволюции была отобрана «классическая» изоформа Pla с повышенной протеолитической активностью, характерная для всех высоковирулентных для человека штаммов Y. pestis subsp. pestis. «Классическая» изоформа Pla Y. pestis функционально подобна активаторам плазминогена млекопитающих, превращающих плазминоген в плазмин путем ограниченного протеолиза. Протеазу Pla, активирующую плазминоген, а также деградирующую основной ингибитор плазмина-α2-антиплазмин и, соответственно, определяющую способность чумного микроба лизировать фибриновые сгустки, препятствующие его распространению после укуса инфицированными блохами или подкожного заражения, принято рассматривать в качестве основного фактора Y. pestis, обеспечивающего генерализацию инфекционного процесса. Pla-опосредованная способность Y. pestis избирательно связываться с внеклеточным матриксом и базальными мембранами может способствовать последующему гидролизу этих структур плазмином хозяина и преодолению патогеном тканевых барьеров. Активатор плазминогена Y. pestis также гидролизует C3 компонент комплемента, человеческий антимикробный пептид-кателицидин LL-37 и такие цитокины как фактор некроза опухолей α, интерферон γ, интерлейкин 8 и протеин 1 хемотаксиса моноцитов. Основной эндогенный ингибитор инициации свертывания крови TFPI, также высокочувствителен к протеолитическому действию Pla, причем эффективность инактивации TFPI гораздо выше, чем эффективность активации плазминогена. В обзоре обсуждается возможность использования Pla в качестве молекулярной мишени для профилактики и лечения чумы.
Biulleten' eksperimental'noĭ biologii i meditsiny, 1995
Molekuliarnaia genetika, mikrobiologiia i virusologiia, 2002
Everlasting reproduction of Yersinia pestis, plague bacillus in natural pestholes needs virulent ... more Everlasting reproduction of Yersinia pestis, plague bacillus in natural pestholes needs virulent causative agent to invade into the host entity, be potent to overcome protection powers of the rodent organism and to pullulate to entail bacteriemia for subsequent conveyance the plague bacillus to the new host by fleas. All of legs of life cyclic patterns of Yersinia pestis are maintained by a number of plague bacillus factors acting jointly or separately, participating at the different stages of infectious process or conveyance. However these factors provide the perpetuation of the plague bacillus in the ecosystems of natural pestholes only acting in conjunction independently on their distinct contributions. Not only biomolecules, organellas and bacteria systems ensured the pursuance of virulent properties, but other factors, essential for survival of Yersinia pestis and the relationship between separate virulence factors and expression of the different genes of housekeeping and virul...
The rough-type lipopolysaccharide (LPS) of the plague pathogen, Yersinia pestis, was studied afte... more The rough-type lipopolysaccharide (LPS) of the plague pathogen, Yersinia pestis, was studied after mild-acid and strong-alkaline degradations by chemical analyses, NMR spectroscopy and electrospray-ionization mass spectrometry, and the following structure of the core region was determined: where L-aD -Hep stands for L-glycero-aD -manno-heptose, Sug1 for either 3-deoxy-aD -manno-oct-2-ulosonic acid (a-Kdo) or D-glycero-aD -talo-oct-2-ulosonic acid (a-Ko), and Sug2 for either b-D-galactose or D-glycero-aD -manno-heptose. A minority of the LPS molecules lacks GlcNAc.
Russian Journal of Infection and Immunity
Genomic, transcriptome or (and) proteomic comparison of closely related virulent and avirulent mi... more Genomic, transcriptome or (and) proteomic comparison of closely related virulent and avirulent microbial strains underlies the search for new pathogenicity factors, potential molecular targets for etiotropic therapy, vaccine prevention and immunotherapy of infectious diseases. This investigation was aimed in testing the ability of method of testicular animalization to select phylogenetically close pairs of Y. pestis strains, which dramatically differ in their pathogenicity for guinea pigs, from the populations of as a rule subcutaneously avirulent for guinea pigs “vole” strains of the plague pathogen. Animalization of Y. pestis cultures were performed on guinea pig males by fourfold testicular passage with reducing infective dose. There was no correlation between the ability to cause generalized infectious process (death) after testicular and subcutaneous infection of guinea pigs, but testicular passages made it possible to enrich bacterial culture with a portion of microbes display...
Immunization with the capsular FI antigen induces protection against
Biomolecules, 2021
Lipopolysaccharide (LPS), localized in the outer leaflet of the outer membrane, serves as the maj... more Lipopolysaccharide (LPS), localized in the outer leaflet of the outer membrane, serves as the major surface component of the Gram-negative bacterial cell envelope responsible for the activation of the host’s innate immune system. Variations of the LPS structure utilized by Gram-negative bacteria promote survival by providing resistance to components of the innate immune system and preventing recognition by TLR4. This review summarizes studies of the biosynthesis of Yersinia pseudotuberculosis complex LPSs, and the roles of their structural components in molecular mechanisms of yersiniae pathogenesis and immunogenesis.
Biomolecules, 2020
Despite the relatively low incidence of plague, its etiological agent, Yersinia pestis, is an exc... more Despite the relatively low incidence of plague, its etiological agent, Yersinia pestis, is an exceptional epidemic danger due to the high infectivity and mortality of this infectious disease. Reports on the isolation of drug-resistant Y. pestis strains indicate the advisability of using asymmetric responses, such as phage therapy and vaccine prophylaxis in the fight against this problem. The current relatively effective live plague vaccine is not approved for use in most countries because of its ability to cause heavy local and system reactions and even a generalized infectious process in people with a repressed immune status or metabolic disorders, as well as lethal infection in some species of nonhuman primates. Therefore, developing alternative vaccines is of high priority and importance. However, until now, work on the development of plague vaccines has mainly focused on screening for the potential immunogens. Several investigators have identified the protective potency of bacte...
Problems of Particularly Dangerous Infections, 2015
Molecular Genetics Microbiology and Virology (Russian version), 2019
Чума-зоонозная инфекция, чей возбудитель был причиной гибели сотен миллионов людей. Широкий круг ... more Чума-зоонозная инфекция, чей возбудитель был причиной гибели сотен миллионов людей. Широкий круг хозяев и переносчиков в сочетании с географической разобщенностью отдельных природных очагов чумы с различными экологическими условиями существования способствуют формированию политипического вида Y. pestis-селекции генетических вариантов, специфичных для определенных природных очагов. Усилиями мирового консорциума исследователей построена согласованная глобальная филограмма SNP-типов чумного микроба, но на просторах России не стихают споры по поводу внутривидовой таксономии Y. pestis. В работе систематики очень много специфического, индивидуального, складывающегося на основе личного опыта. Здесь важно умение следовать старому правилу, требующему, чтобы границы проводили там, где их провела природа, и не проводили там, где она их не проводила. Исходя из этого, мы предлагаем рациональный вариант приведения номенклатуры чумного микроба в соответствие с правилами Международного кодекса номенклатуры бактерий и эволюционной таксономии.
PloS one, 2016
It has been shown previously that several endemic Y. pestis isolates with limited virulence conta... more It has been shown previously that several endemic Y. pestis isolates with limited virulence contained the I259 isoform of the outer membrane protease Pla, while the epidemic highly virulent strains possessed only the T259 Pla isoform. Our sequence analysis of the pla gene from 118 Y. pestis subsp. microtus strains revealed that the I259 isoform was present exclusively in the endemic strains providing a convictive evidence of more ancestral origin of this isoform. Analysis of the effects of the I259T polymorphism on the intrinsic disorder propensity of Pla revealed that the I259T mutation slightly increases the intrinsic disorder propensity of the C-terminal tail of Pla and makes this protein slightly more prone for disorder-based protein-protein interactions, suggesting that the T259 Pla could be functionally more active than the I259 Pla. This assumption was proven experimentally by assessing the coagulase and fibrinolytic activities of the two Pla isoforms in human plasma, as well...
Advances in experimental medicine and biology, 2016
Plague still poses a significant threat to human health and as a reemerging infection is unfamili... more Plague still poses a significant threat to human health and as a reemerging infection is unfamiliar to the majority of the modern medical doctors. In this chapter, the plague is described according to Dr. Nikiforov's experiences in the diagnosis and treatment of patients, and also a review of the relevant literature on this subject is provided. The main modern methods and criteria for laboratory diagnosis of plague are briefly described. The clinical presentations include the bubonic and pneumonic form, septicemia, rarely pharyngitis, and meningitis. Early diagnosis and the prompt initiation of treatment reduce the mortality rate associated with bubonic plague and septicemic plague to 5-50 %; although a delay of more than 24 h in the administration of antibiotics and antishock treatment can be fatal for plague patients. Most human cases can successfully be treated with antibiotics.
Journal of biomolecular structure & dynamics, Jan 3, 2016
The Yersinia pestis outer membrane porin F (OmpF) is a transmembrane protein located in the outer... more The Yersinia pestis outer membrane porin F (OmpF) is a transmembrane protein located in the outer membrane of this Gram-negative bacterium which is the causative agent of plague, where it plays a significant role in controlling the selective permeability of the membrane. The amino acid sequences of OmpF proteins from 48 Y. pestis strains representing all currently available phylogenetic groups of this Gram-negative bacterium were recently deduced. Comparison of these amino acid sequences revealed that the OmpF can be present in four isoforms, the pestis-pestis type, and the pestis-microtus types I, II, and III. OmpF of the most recent pestis-pestis type has an alanine residue at the position 148, where all the pestis-microtus types have threonine there (T148A polymorphism). The variability of different pestis-microtus types is caused by an additional polymorphism at the 193rd position, where the OmpFs of the pestis-microtus type II and type III have isoleucine-glycine (IG(+)193) or ...
PloS one, 2016
Yersinia pestis Caf1 is a multifunctional protein responsible for antiphagocytic activity and is ... more Yersinia pestis Caf1 is a multifunctional protein responsible for antiphagocytic activity and is a key protective antigen. It is generally conserved between globally distributed Y. pestis strains, but Y. pestis subsp. microtus biovar caucasica strains circulating within populations of common voles in Georgia and Armenia were reported to carry a single substitution of alanine to serine. We investigated polymorphism of the Caf1 sequences among other Y. pestis subsp. microtus strains, which have a limited virulence in guinea pigs and in humans. Sequencing of caf1 genes from 119 Y. pestis strains belonging to different biovars within subsp. microtus showed that the Caf1 proteins exist in three isoforms, the global type Caf1NT1 (Ala48 Phe117), type Caf1NT2 (Ser48 Phe117) found in Transcaucasian-highland and Pre-Araks natural plague foci #4-7, and a novel Caf1NT3 type (Ala48 Val117) endemic in Dagestan-highland natural plague focus #39. Both minor types are the progenies of the global iso...
Russian Journal of Infection and Immunity, 2015
Резюме. Чума была причиной трех пандемий и привела к гибели миллионов людей. Чума-типичный зооноз... more Резюме. Чума была причиной трех пандемий и привела к гибели миллионов людей. Чума-типичный зооноз, и ее возбудитель-Yersinia pestis, циркулирует в популяциях диких грызунов, обитающих в природных очагах чумы на всех материках, кроме Австралии. Передача чумы осуществляется укусами блох. Циркуляция Y. pestis в природных очагах чумы обеспечивается целым рядом факторов патогенности. В обзоре рассматривается один из них-активатор плазминогена Pla. Этот белок является одним из представителей омптинов-семейства протеаз наружных мембран патогенных энтеробактерий, обеспечивающих колонизацию отдельных органов и даже генерализацию инфекции в результате успешного противостояния врожденному иммунитету хозяина. Описаны история открытия, генетический контроль, условия биосинтеза, выделение, очистка и физико-химические свойства активатора плазминогена. Высокоочищенные препараты активатора плазминогена утрачивают свою ферментативную активность, а ренатурация в присутствии липоолигосахарида Y. pestis восстанавливает энзиматические свойства Pla. Этот фактор патогенности отсутствует у наиболее древней филогенетической группы чумного микроба, bv. caucasica, а предшественник остальных групп Y. pestis subsp. microtus получил в результате горизонтального переноса изоформу Pla, близкую по свойствам омптинам менее вирулентных энтеробактерий. Затем в ходе микроэволюции была отобрана «классическая» изоформа Pla с повышенной протеолитической активностью, характерная для всех высоковирулентных для человека штаммов Y. pestis subsp. pestis. «Классическая» изоформа Pla Y. pestis функционально подобна активаторам плазминогена млекопитающих, превращающих плазминоген в плазмин путем ограниченного протеолиза. Протеазу Pla, активирующую плазминоген, а также деградирующую основной ингибитор плазмина-α2-антиплазмин и, соответственно, определяющую способность чумного микроба лизировать фибриновые сгустки, препятствующие его распространению после укуса инфицированными блохами или подкожного заражения, принято рассматривать в качестве основного фактора Y. pestis, обеспечивающего генерализацию инфекционного процесса. Pla-опосредованная способность Y. pestis избирательно связываться с внеклеточным матриксом и базальными мембранами может способствовать последующему гидролизу этих структур плазмином хозяина и преодолению патогеном тканевых барьеров. Активатор плазминогена Y. pestis также гидролизует C3 компонент комплемента, человеческий антимикробный пептид-кателицидин LL-37 и такие цитокины как фактор некроза опухолей α, интерферон γ, интерлейкин 8 и протеин 1 хемотаксиса моноцитов. Основной эндогенный ингибитор инициации свертывания крови TFPI, также высокочувствителен к протеолитическому действию Pla, причем эффективность инактивации TFPI гораздо выше, чем эффективность активации плазминогена. В обзоре обсуждается возможность использования Pla в качестве молекулярной мишени для профилактики и лечения чумы.
Biulleten' eksperimental'noĭ biologii i meditsiny, 1995
Molekuliarnaia genetika, mikrobiologiia i virusologiia, 2002
Everlasting reproduction of Yersinia pestis, plague bacillus in natural pestholes needs virulent ... more Everlasting reproduction of Yersinia pestis, plague bacillus in natural pestholes needs virulent causative agent to invade into the host entity, be potent to overcome protection powers of the rodent organism and to pullulate to entail bacteriemia for subsequent conveyance the plague bacillus to the new host by fleas. All of legs of life cyclic patterns of Yersinia pestis are maintained by a number of plague bacillus factors acting jointly or separately, participating at the different stages of infectious process or conveyance. However these factors provide the perpetuation of the plague bacillus in the ecosystems of natural pestholes only acting in conjunction independently on their distinct contributions. Not only biomolecules, organellas and bacteria systems ensured the pursuance of virulent properties, but other factors, essential for survival of Yersinia pestis and the relationship between separate virulence factors and expression of the different genes of housekeeping and virul...