Genome-wide Mycobacterium tuberculosis variation (GMTV) database: a new tool for integrating sequence variations and epidemiology.

BACKGROUND: Tuberculosis (TB) poses a worldwide threat due to advancing multidrug-resistant strains and deadly co-infections with Human immunodeficiency virus. Today large amounts of Mycobacterium tuberculosis whole genome sequencing data are being assessed broadly and yet there exists no comprehensive online resource that connects M. tuberculosis genome variants with geographic origin, with drug resistance or with clinical outcome. DESCRIPTION: Here we describe a broadly inclusive unifying Genome-wide Mycobacterium tuberculosis Variation (GMTV) database, (http://mtb.dobzhanskycenter.org) that catalogues genome variations of M. tuberculosis strains collected across Russia. GMTV contains a broad spectrum of data derived from different sources and related to M. tuberculosis molecular biology, epidemiology, TB clinical outcome, year and place of isolation, drug resistance profiles and displays the variants across the genome using a dedicated genome browser. GMTV database, which includes 1084 genomes and over 69,000 SNP or Indel variants, can be queried about M. tuberculosis genome variation and putative associations with drug resistance, geographical origin, and clinical stages and outcomes. CONCLUSIONS: Implementation of GMTV tracks the pattern of changes of M. tuberculosis strains in different geographical areas, facilitates disease gene discoveries associated with drug resistance or different clinical sequelae, and automates comparative genomic analyses among M. tuberculosis strains.

Ensemble density-dependent synchronization of mycobacterial growth: BACTEC MGIT 960 fluorescence-based analysis and mathematical modelling of coupled biophysical and chemical processes.

This study presents an analysis of M. tuberculosis growth data obtained using the BACTEC MGIT 960 system and respective mathematical models. The system is based on the detection of a decrease in oxygen level in the broth due to the bacterial respiration. It is shown that recordings sampled with a 1 hour rate provide an opportunity to distinguish between the oxygen consumption of growing cells and active cells division when the density of micro-organisms is sufficient to enter into the synchronized division mode. More specifically, the growth of culture is continuous only with large initial dilutions; otherwise, there are jumps between different growth stages with a time interval of 13-15 h. The combination of the oxygen-quenching kinetics for an analytic reagent and the population growth kinetics resulted in a mathematical model, which consists of mixing Verhulst's and Gompertz's models. The parameters of such mixing and switching between the models' prevalences are discussed with respect to oxygen uptake reactions reflected in the changes in the experimentally registered fluorescence level.

Bi-logistic model for disease dynamics caused by Mycobacterium tuberculosis in Russia.

In this work, we explore epidemiological dynamics by the example of tuberculosis in Russian Federation. It has been shown that the epidemiological dynamics correlates linearly with the virulence of Mycobacterium tuberculosis during the period 1987-2012. To construct an appropriate model, we have analysed (using LogLet decomposition method) epidemiological World Health Organization (WHO) data (period 1980-2014) and obtained, as result of their integration, a curve approximated by a bi-logistic function. This fact allows a subdivision of the whole population into parts, each of them satisfies the Verhulst-like models with different constant virulences introduced into each subsystem separately. Such a subdivision could be interconnected with the heterogeneous structure of mycobacterial population that has a high ability of adaptation to the host and strong mutability.

Genetic diversity of the Mycobacterium tuberculosis Beijing family in Brazil and Mozambique and relation with infectivity and induction of necrosis in THP-1 cells.

INTRODUCTION: The success of the Mycobacterium tuberculosis Beijing (MtbB) lineage in different geographical regions has been attributed to high transmission, increased virulence, drug resistance and rapid adaptation to the host. In some countries of secondary MtbB dispersion like South Africa and Peru, rising prevalence of the Beijing strains is registered. However, in neighboring countries to affected regions such as Mozambique and Brazil, respectively, the prevalence of these strains is still low and this could be due to biological particularities of the circulating MtbB strains and/or differentiated host susceptibility. OBJECTIVE: To characterize genetically and phenotypically MtbB strains isolated in Brazil (n = 8) and Mozambique (n = 17). METHODS: This is a descriptive study of genotypes of the MtbB isolates, determined by spoligotyping, MIRU-VNTR typing, analysis of the IS6110 copy number in the NTF region and screening for mutations in mutT2, mutT4, rpoB, katG and pks 15/1 genes. Virulence-associated properties of the studied isolates were verified in the in vitro model of infection of human THP-1 cells. RESULTS: The genotypes defined by the 24VNTRs were distinct for all isolates included in this study and presented an HGDI of 0.997. The VNTR patterns with seven copies of MIRU26 and seven copies of QUB26, representative for the previously described MtbB genotype B0, dominant in Russia, were detected in 38.5% of the studied isolates. In addition, all isolates presented RD105 deletion and a 7 bp insertion in pks15/1 gene. Almost all tested strains belonged to the RD181 sublineage, with the exception of two strains from Mozambique of RD150 sublineage. Combined analysis of the NTF region integrity and mutations in mutT genes showed that 62.5% and 47% of isolates obtained in Brazil and Mozambique, respectively, were of the ancestral genotype. The virulence index of the ancient isolates, evaluated in the THP-1 cells, was significantly lower than that of the modern genotype group. CONCLUSIONS: These data demonstrate genotype particularities of the Beijing strains isolated in Brazil and Mozambique, two countries of low prevalence of the MtbB lineage in local Mtb populations. In contrast to the neighboring countries with high prevalence of the MtbB strains of modern sublineage, significant proportions of the isolates obtained in Brazil and Mozambique were presented by the strains of the ancient sublineage. Our data suggest that lower virulence of the ancient strains, compared with the modern strains, could be involved in the slow spread of the MtbB strains in some regions.