Saint Petersburg, Russia
Saint Petersburg, Russia

Time filter

Source Type

Mokrousov I.,St Petersburg Pasteur Institute
Tuberculosis | Year: 2017

Hunter Gaston Discriminatory Index (HGDI) is a widely used estimator of discriminatory power of genotyping methods and diversity of molecular markers in bacterial pathogens, including Mycobacterium tuberculosis. In my opinion, the index is somewhat misleading: a closer look at common practice and particular studies reveals that values in the range of 0.6–0.9 are modest but uncritically perceived as high. I propose and discuss three courses of change: (i) to continue using HGDI but be aware of the true meaning behind its value and increase a threshold of acceptable resolution to the more adequate values of 0.90–0.99, depending on study design; (ii) to turn to other known indices of diversity (e.g., Shannon index), in order to complement HGDI; (iii) to develop new, intuitively more realistic estimator. © 2017 Elsevier Ltd

Garcia De Viedma D.,Hospital General Universitario Gregorio Maranon | Garcia De Viedma D.,CIBER ISCIII | Mokrousov I.,St Petersburg Pasteur Institute | Rastogi N.,Institute Pasteur Of Guadeloupe Morne Joliviere
Enfermedades Infecciosas y Microbiologia Clinica | Year: 2011

The application of genotyping tools to the analysis of tuberculosis (TB) has allowed us to identify clinical isolates of Mycobacterium tuberculosis to strain level. M. tuberculosis fingerprinting has been applied at different levels: a) in the laboratory, to optimize identification of cross-contamination events which can lead to a false diagnosis; b) in the patient, to determine whether recurrences are due to reactivations or exogenous reinfections or to identify cases coinfected by more than one strain; c) at the micropopulation level, to identify clusters of cases infected by the same strains (recent transmission) and to differentiate them from orphan cases that are most probably due to reactivations; and d) at the macropopulation level, to define the global distribution of M. tuberculosis lineages, to monitor the international spread of high-risk strains, and to explore the evolutionary features of M. tuberculosis. In recent years, important methodological and strategic advances have been applied at these different levels of analysis. Rather than provide an exhaustive review, the present study focuses on specific advances in micropopulation and macropopulation analysis. © 2011 Elsevier España S.L.

Ribeiro S.C.M.,State University of Norte Fluminense | Gomes L.L.,Instituto Oswaldo Cruz | Amaral E.P.,University of Sao Paulo | Andrade M.R.M.,State University of Norte Fluminense | And 7 more authors.
Journal of Clinical Microbiology | Year: 2014

Strains of the Beijing genotype family of Mycobacterium tuberculosis are a cause of particular concern because of their increasing dissemination in the world and their association with drug resistance. Phylogenetically, this family includes distinct ancient and modern sublineages. The modern strains, contrary to the ancestral counterparts, demonstrated increasing prevalence in many world regions that suggest an enhanced bacterial pathogenicity. We therefore evaluated virulence of modern versus ancient Beijing strains with similar epidemiological and genotype characteristics. For this, we selected six strains that had very similar 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat (MIRU-VNTR) typing profiles and belonged to the region of difference 181 (RD181) subgroup but differed using markers (mutT2 and mutT4 genes and NTF locus) that discriminate between modern and ancient Beijing sublineages. The strains were isolated from native patients in Brazil and Mozambique, countries with a low prevalence of Beijing strains. The virulence levels of these strains were determined in models of pulmonary infection in mice and in vitro macrophage infection and compared with that of a strain from Russia, part of the epidemic and hypervirulent Beijing clone B0/W148, and of the laboratory strain H37Rv. The results showed that two of the three modern Beijing strains were highly pathogenic, exhibiting levels of virulence comparable with that of the epidemic Russian strain. In contrast, all isolates of the ancient sublineage displayed intermediate or low virulence. The data obtained demonstrate that the strains of the modern Beijing sublineage are more likely to exhibit highly virulent phenotypes than ancient strains and suggest that genetic alterations characteristic of the modern Beijing sublineage favor selection of highly virulent bacteria. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Valcheva V.,Bulgarian Academy of Science | Mokrousov I.,St Petersburg Pasteur Institute
Biotechnology and Biotechnological Equipment | Year: 2011

Emergence of multidrug-resistant Mycobacterium tuberculosis strains and their global dissemination necessitate development, evaluation and comparison of the rapid molecular tests that target genetic determinants of bacterial drug resistance. A wide range of such methods is available at present and the choice of those most appropriate is among the pertinent tasks of the National Tuberculosis Control Programs. Inadequate and/or interrupted therapy allows the selection of spontaneous mutations in favor of resistant organisms while sequential acquisition of these mutations in different genome loci results in the development of resistance to multiple drugs. The standard DOTS course comprises the five first-line drugs: rifampin (RIF), isoniazid (INH), streptomycin (STR), ethambutol (EMB), and pyrazinamide (PZA). Multi-drug resistance (MDR) is defined as resistance to at least RIF and INH. Anti-TB drug resistance is characterized by multigenic (rpoB, katG, inhA, ndh, embB, rpsL, rrs, pncA, gyrA) control and geographic variation of resistance mutations. Correct and rapid detection of drug resistance facilitates the appropriate and timely delivery of anti-TB therapy and reduces overall treatment cost. The prediction of drug resistance of M. tuberculosis by molecular tools presents a rapid alternative to the culture-based phenotypic susceptibility tests. Among the genotypic methods used to date are direct sequencing, microchips technology, PCR-single strand conformation polymorphism, RNA/RNA mismatch, molecular beacons and other assays. Genotypic methods allow rapid prediction of resistance to main anti- TB drugs in the considerable proportion of M. tuberculosis strains circulating in areas with high burden of MDR-TB.

Demay C.,Institute Pasteur Of Guadeloupe | Liens B.,Institute Pasteur Of Guadeloupe | Burguiere T.,Institute Pasteur Of Guadeloupe | Hill V.,Institute Pasteur Of Guadeloupe | And 6 more authors.
Infection, Genetics and Evolution | Year: 2012

Among various genotyping methods to study Mycobacterium tuberculosis complex (MTC) genotypic polymorphism, spoligotyping and mycobacterial interspersed repetitive units-variable number of DNA tandem repeats (MIRU-VNTRs) have recently gained international approval as robust, fast, and reproducible typing methods generating data in a portable format. Spoligotyping constituted the backbone of a publicly available database SpolDB4 released in 2006; nonetheless this method possesses a low discriminatory power when used alone and should be ideally used in conjunction with a second typing method such as MIRU-VNTRs for high-resolution epidemiological studies. We hereby describe a publicly available international database named SITVITWEB which incorporates such multimarker data allowing to have a global vision of MTC genetic diversity worldwide based on 62,582 clinical isolates corresponding to 153 countries of patient origin (105 countries of isolation). We report a total of 7105 spoligotype patterns (corresponding to 58,180 clinical isolates) - grouped into 2740 shared-types or spoligotype international types (SIT) containing 53,816 clinical isolates and 4364 orphan patterns. Interestingly, only 7% of the MTC isolates worldwide were orphans whereas more than half of SITed isolates (n=27,059) were restricted to only 24 most prevalent SITs. The database also contains a total of 2379 MIRU patterns (from 8161 clinical isolates) from 87 countries of patient origin (35 countries of isolation); these were grouped in 847 shared-types or MIRU international types (MIT) containing 6626 isolates and 1533 orphan patterns. Lastly, data on 5-locus exact tandem repeats (ETRs) were available on 4626 isolates from 59 countries of patient origin (22 countries of isolation); a total of 458 different VNTR patterns were observed - split into 245 shared-types or VNTR International Types (VIT) containing 4413 isolates) and 213 orphan patterns. Datamining of SITVITWEB further allowed to update rules defining MTC genotypic lineages as well to have a new insight into MTC population structure and worldwide distribution at country, sub-regional and continental levels. At evolutionary level, the data compiled may be useful to distinguish the occasional convergent evolution of genotypes versus specific evolution of sublineages essentially influenced by adaptation to the host. This database is publicly available at: © 2012 Elsevier B.V..

Mokrousov I.,St Petersburg Pasteur Institute
Infection, Genetics and Evolution | Year: 2012

The absence of lateral gene exchange is a characteristic feature defining the genome evolution and clonal population structure of Mycobacterium tuberculosis. Certain of its lineages have justly attracted more attention due to their global dissemination and/or remarkable pathogenic properties. In this critical review, I discuss the population structure and genetic geography of the less 'popular' but in some aspects no less noteworthy M. tuberculosis lineage, Ural family. Its specific signature was initially defined by single copy in MIRU26, and large (>6) copy number in MIRU10 loci, and by 43-spoligotyping as absence of signals 29-31 and 33-36. Here, I suggest to subdivide Ural strains with present and absent spoligosignal 2 into primary Ural-1 and secondary Ural-2 sublineages, respectively, while 1 copy in MIRU26 is specific of Ural-1. Furthermore, three copies were recently described in MIRU10 in Ural-1 strains which highlights a high diversity of this locus in Ural genotype. The data on the two Ural sublineages were extracted from SpolDB4 database and original publications in order to trace their distribution at global and within-country levels. Importantly, the rigorous reanalysis suggested the true rate of the Ural genotype in the Ural area in Russia to be only 7%. In contrast, the frequencies of the Ural sublineages peak elsewhere: in South Ukraine and Georgia/Abkhazia (Ural-1, up to 14-19%), and in southwestern Iran (Ural-2, up to 26%). However, as this name is used since 2005, it seems most parsimonious to continue its use even if misleading. The forest graph was built on the available spoligoprofiles of Ural family strains from Eurasia. It helped to suggest routes of their primary dispersal that are discussed in the context of the known human migrations also influenced by natural barriers. The north/east Pontic area may have been an area of origin and primary dispersal of the Ural (Ural-1) genotype in Eurasia, whereas political and natural borders may have influenced its subsequent dissemination throughout Central Asia. Studies of phenotypic properties in different models, comparison with host genetics give evidence that the Ural family strains are not associated with increased capacity to acquire drug resistance, pathogenicity or transmissibility. Instead since Ural family is rather moderately widespread in Eurasia beyond the hypothesized areas of origin, this situation may be a result of its low contagiosity as a consequence of long-term co-adaptation with human host. Future research should be focused on whole-genome sequencing in order to identify Ural-specific SNP and/or deletion, to resolve its phylogenetic and phylogeographic uncertainty and to elucidate biological features underlying its circulation and co-evolution with the human species. © 2011 Elsevier B.V..

The increase in tick-borne encephalitis (TBE) incidence is observed in recent decades in a number of subarctic countries. The reasons of it are widely discussed in scientific publications. The objective of this study was to understand if the climate change in Arkhangelsk Oblast (AO) situated in the north of European subarctic zone of Russia has real impact on the northward expansion of Ixodid ticks and stipulates the increase in TBE incidence. This study analyzes: TBE incidence in AO and throughout Russia, the results of Ixodid ticks collecting in a number of sites in AO, and TBE virus prevalence in those ticks, the data on tick bite incidence in AO, and meteorological data on AO mean annual air temperatures and precipitations. It is established that in recent years TBE incidence in AO tended to increase contrary to its apparent decrease nationwide. In last 10 years, there was nearly 50-fold rise in TBE incidence in AO when compared with 1980-1989. Probably, the increase both in mean annual air temperatures and temperatures during tick active season resulted in the northward expansion of Ixodes Persulcatus, main TBE virus vector. The Ixodid ticks expansion is confirmed both by the results of ticks flagging from the surface vegetation and by the tick bite incidence in the population of AO locations earlier free from ticks. Our mathematical (correlation and regression) analysis of available data revealed a distinct correlation between TBE incidence and the growth of mean annual air temperatures in AO in 1990-2009. Not ruling out other factors, we conclude that climate change contributed much to the TBE incidence increase in AO. © 2011 N. K. Tokarevich et al.

Kalinina O.V.,St Petersburg Pasteur Institute
Voprosy Virusologii | Year: 2015

Hepatitis C virus (HCV) is one of the most dynamically evolving viral pathogens. In the last decade extensive molecular epidemiological studies demonstrated great HCV diversity. This review describes the HCV variability mechanisms and the current HCV classification, presents data on the geographical spread of different HCV subtypes and its evolution, including natural recombinant forms.

Mokrousov I.,St Petersburg Pasteur Institute
Clinical Microbiology Reviews | Year: 2013

Mycobacterium tuberculosis variant Beijing B0/W148 is regarded as a successful clone of M. tuberculosis that is widespread in the former Soviet Union and respective immigrant communities. Understanding the pathobiology and phylogeography of this notorious strain may help to clarify its origin and evolutionary history and the driving forces behind its emergence and current dissemination. I present the first review and analysis of all available data on the subject. In spite of the common perception of the omnipresence of B0/W148 across post-Soviet countries, its geographic distribution shows a peculiar clinal gradient. Its frequency peaks in Siberian Russia and, to a lesser extent, in the European part of the former Soviet Union. In contrast, the frequency of B0/W148 is sharply decreased in the Asian part of the former Soviet Union, and it is absent in autochthonous populations elsewhere in the world. Placing the molecular, clinical, and epidemiological features in a broad historical, demographic, and ecological context, I put forward two interdependent hypotheses. First, B0/W148 likely originated in Siberia, and its primary dispersal was driven by a massive population outflow from Siberia to European Russia in the 1960s to 1980s. Second, a historically recent, phylogenetically demonstrated successful dissemination of the Beijing B0/W148 strain was triggered by the advent and wide use of modern antituberculosis (anti-TB) drugs and was due to the remarkable capacity of this strain to acquire drug resistance. In contrast, there is some indication, but not yet systematic proof, of an enhanced virulence of this strain. © 2013, American Society for Microbiology. All Rights Reserved.

Here, I review the population structure and phylogeography of the two contrasting families of Mycobacterium tuberculosis, Beijing and Ural, in the context of strain pathobiology and human history and migration. Proprietary database (12-loci MIRU-VNTR profiles of 3067 Beijing genotype isolates) was subjected to phylogenetic and statistical analysis. The highest rate (90%) and diversity (HGI 0.80-0.95) of the Beijing genotype in North China suggest it to be its area of origin. Under VNTR-based MDS analysis the interpopulation genetic distances correlated with geography over uninterrupted landmasses. In contrast, large water distances together with long time generated remarkable outliers. Weak and less expected affinities of the distant M. tuberculosis populations may reflect hidden epidemiological links due to unknown migration. Association with drug-resistance or increased virulence/transmissibility along with particular human migration flows shape global dissemination of some Beijing clones. The paucity of data on the Ural genotype prevents from high-resolution analysis that was mainly based on the available spoligotyping data. The North/East Pontic area marked with the highest prevalence of the Ural family may have been the area of its origin and primary dispersal in Eurasia. Ural strains are not marked by increased pathogenic capacities, increased transmissibility and association with drug resistance (but most recent reports describe an alarming increase of MDR Ural strains in some parts of eastern Europe and northwestern Russia). Large-scale SNP or WGS population-based studies targeting strains from indigenous populations and, eventually, analysis of ancient DNA will better test these hypotheses. Host genetics factors likely play the most prominent role in differential dissemination of particular M. tuberculosis genotypes. © 2015 Elsevier Ltd. All rights reserved.

Loading St Petersburg Pasteur Institute collaborators
Loading St Petersburg Pasteur Institute collaborators