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The dramatic change in global health imposed by the Covid-19 pandemic has also impacted TB control. The TB incidence decreased dramatically not because of the improved situation but due to undertesting, reduced resources, and ultimately, substantially reduced detection rate. We hypothesized that multiple and partly counteracting factors could influence changes in the local Mycobacterium tuberculosis population. To test this hypothesis, we analyzed M. tuberculosis isolates collected in Western Siberia, Russia, before and during the Covid-19 pandemic. A total of 269 M. tuberculosis isolates from patients admitted at referral clinics were studied. The pre-pandemic and pandemic collections included 179 and 90 isolates, respectively. Based on genotyping, both pre-pandemic and pandemic samples are heavily dominated by the Beijing genotype isolates (95% and 88%) that were mostly MDR (80 and 68%). The high proportion of MDR isolates is due to the specific features of the studied collections biased towards patients with severe TB admitted at the National referral center in Novosibirsk. While no dramatic change was observed in the M. tuberculosis population structure in the survey area in Western Siberia during the Covid-19 pandemic in 2020-2021 compared to the pre-pandemic collection, still we note a certain decrease of the Beijing genotype and an increase in the proportion and diversity of the non-Beijing isolates. However, the transmissible and MDR Beijing B0/W148 did not increase its prevalence rate during the pandemic. More generally, the high prevalence rate of the Beijing genotype and its strong association with MDR both before and during the pandemic are alarming features of this region in Western Siberia, Russia., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The aim of this study was to perform a molecular characterization of Mycobacterium tuberculosis strains circulating in one of the "closed" Russian cities under conditions of the limited population migration and high HIV coinfection rate. We analyzed 109 M. tuberculosis isolates recovered from TB patients in the Novouralsk municipality in the Ural area of Russia; 38.5% were from HIV coinfected TB patients and 19.3% patients were former prison inmates. The Beijing genotype was predominant (78.9%) while 57.8% and 17.4% of isolates belonged to the Beijing B0/W148 and Beijing 94-32-clusters, respectively. An atypical allele of the QUB26 VNTR locus (2 repeat units) was detected in 11 of 63 Beijing B0/W148 isolates. The non-Beijing isolates were subdivided into nine spoligotypes of the four genetic families (Ural, LAM, Haarlem, T), SIT35/Ural being the largest group (n = 9; 8.3%). Multidrug resistance (MDR) was detected in 63.6% and 83.7% of isolates from newly diagnosed and previously treated patients, respectively. Almost all isolates of the B0/W148-cluster were MDR (92.1%) compared to the Beijing 94-32-cluster (47.4%). No association was found between HIV status of patients and MDR-TB or particular genetic cluster. A combined contact and molecular investigation confirmed three family foci; in two of them, Ural SIT35 and Beijing B0/W148 strains were transmitted from HIV-infected sons to their fathers. To conclude, M. tuberculosis population in Novouralsk features an exceptionally high prevalence of the strongly MDR Beijing B0/W148-cluster and emergence of the B0/W148 substrain with unusual QUB26 allele. This situation was likely synergistically shaped by the limited population migration, high prevalence of the HIV coinfection and high proportion of the former prisoners. The existing organizational approaches to prevent TB transmission are insufficient and require a serious revision., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Albania is a Balkan country with moderate to low incidence of tuberculosis (TB) and very low prevalence of drug resistant TB. Here, we analyzed a country-wide multi-year Mycobacterium tuberculosis collection in order to detect possible dynamic trends of TB in Albania, with a focus on drug resistance and endemic/epidemic clones. In total, 743 isolates collected in 2007 to 2011 were divided into 107 spoligotypes and 351 MIRU-types. Based on the MIRU-VNTR phylogenetic analysis, the isolates were assigned to the following lineages/families: animal ecotypes (5 M. bovis and 2 M. caprae isolates), Lineage 2 (5 Beijing isolates), Lineage 3 (1 CAS-Delhi isolate) and, mostly and overwhelmingly, Lineage 4 (Cameroon, Uganda, Ghana and related; NEW-1-related; Ural, Haarlem, LAM, S, TUR; and unclassified isolates). Most of the isolates (452/743) were intermediately located on the global VNTR tree and did not cluster with any reference profile; they were distantly related to different families within Lineage 4 and we designated them as "unclassified L4" isolates. The significantly higher proportion of drug resistance was observed in (i) Beijing genotype compared to all other isolates (60%, P = .008), (ii) "unclassified L4" compared to all other isolates (13.9%, P = .04) and (iii) SIT2936 compared to other "unclassified L4" (34.3%, P = .0006). Analysis of the yearly collections revealed (i) some decrease of the large heterogeneous "unclassified L4" from 65% to 57%; (ii) steadily increasing gradient of LAM from 3.4 to 13.3%; (iii) stable prevalence of Haarlem (15-20%); and (iv) decrease of TUR with only 1.1% in 2011. Most of the LAM (33/49) and Beijing (3/5) isolates belonged to the VNTR types specific for Russia and former Soviet Union countries. To conclude, our results highlight a peculiar nature of M. tuberculosis population in Albania that is dominated by local and unclassified genotypes within Lineage 4, and also features European genotypes and epidemically relevant clones originating from the former Soviet Union countries. At the same time, these imported clones remain drug susceptible and prevalence of drug resistance on a whole is low., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interests., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Japan reportedly has high incidence rate of nontuberculous mycobacterial lung disease (14.7 cases per 100,000 person in 2014). In Japan, the most common etiology is Mycobacterium avium subsp. hominissuis (MAH). MAH is a typical inhabitant of the environment, especially bathrooms, which are considered as a potential source of infection. To corroborate this hypothesis, we determined the detection rate of MAH in bathrooms of healthy volunteers by an ordinary culture method and we analyzed the genetic relatedness of these isolates with those from patients and other sources. We collected swabs of bathtub inlets, showerheads, bathroom drains, and shower water from 180 residences throughout Japan. The overall MAH detection rate was 16.1%, but the rate varied among regions: it was high in Kanto (9/34, 26.5%) and Kinki (9/33, 27.3%), but low in Kyushu (0/11, 0%), Tohoku (1/23, 4.3%), and Hokkaido (2/23, 8.7%). MAH was detected primarily in bathtub inlet samples (25 out of 170 residences). Variable numbers of tandem repeats (VNTR) analysis was used to examine the genetic relatedness of 57 MAH isolates from bathrooms of the healthy volunteers with human clinical isolates. A minimum spanning tree generated on the basis of the VNTR data indicated that isolates from the bathrooms of the healthy volunteers had a high degree of genetic relatedness with those from Japanese patients, bathrooms of patients, and river water, but not with those from Russian patients and Japanese pigs. These results showed that bathtub inlets in Japan provide an environmental niche for MAH and suggest that bathrooms are one of the important infection sources of MAH in Japan. Understanding country-specific lifestyle habits, such as bathing in Japan, as well as the genetic diversity of MAH, will help in elucidating the sources of this pathogen., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The 2nd St. Petersburg Symposium on Tuberculosis and Mycobacteria: Molecular Approach, was held in St. Petersburg, Russia on 5-6 December 2018. A special issue of Infection, Genetics and Evolution will publish articles based on the selected presentations. In this paper, I will discuss some of the hot topics of molecular mycobacteriology highlighted at this meeting that I had the pleasure to organize and honor to chair. The symposium addressed interrelated fundamental and applied issues of modern mycobacteriology such as molecular evolution and phylogenomics, host-microbe interactions and pathogenesis, coevolution of M. tuberculosis with humans, new genomic and postgenomic technologies. Molecular methods for TB diagnostics and drug resistance detection are supported by WHO and whole genome/next generation sequencing presents a comprehensive approach. At the same time, cost and implementation of new methods for direct analysis of clinical samples and/or in low-resource settings remain a great challenge. A due attention was also given to the medically important nontuberculous mycobacteria. Assessment of spectrum of the circulating mycobacterial species in the Russian Federation and the countries of the European Union was presented and the underlying reasons of the observed diversity were discussed. To conclude, the symposium became a multidisciplinary event that was useful to promote networking and exchange of knowledge and experience. The next (third) symposium was planned to be organized in 2021., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Tuberculosis (TB) remains a major health problem within the Community of Portuguese Language Speaking Countries (CPLP). Despite the marked variation in TB incidence across its member-states and continued human migratory flux between countries, a considerable gap in the knowledge on the Mycobacterium tuberculosis population structure and strain circulation between the countries still exists. To address this, we have assembled and analysed the largest CPLP M. tuberculosis molecular and drug susceptibility dataset, comprised by a total of 1447 clinical isolates, including 423 multidrug-resistant isolates, from five CPLP countries. The data herein presented reinforces Latin American and Mediterranean (LAM) strains as the hallmark of M. tuberculosis populational structure in the CPLP coupled with country-specific differential prevalence of minor clades. Moreover, using high-resolution typing by 24-loci MIRU-VNTR, six cross-border genetic clusters were detected, thus supporting recent clonal expansion across the Lusophone space. To make this data available to the scientific community and public health authorities we developed CPLP-TB (available at http://cplp-tb.ff.ulisboa.pt), an online database coupled with web-based tools for exploratory data analysis. As a public health tool, it is expected to contribute to improved knowledge on the M. tuberculosis population structure and strain circulation within the CPLP, thus supporting the risk assessment of strain-specific trends., (Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.)

Selective pressure from antibiotic use is one of the most important risk factors associated with the development of drug resistance in Mycobacterium tuberculosis (MTB). However, the mechanisms underlying drug resistance at the molecular level remain partly unclear. Therefore, the purpose of this study was to investigate the potential functional effect of novel mutations arising from anti-tuberculosis treatment. We analyzed two multidrug-resistant TB (MDR-TB) isolates from the same patient; one collected before and one almost a year after commencing MDR-TB treatment. The post-treatment isolate exhibited elevated ethambutol resistance. We sequenced the whole genomes of the two clinical isolates and detected six novel polymorphisms affecting the genes Rv1026, nc0021, Rv2155c, Rv2437, and Rv3696c, and the intergenic region between Rv2764c and Rv2765. Metabolomics approach was used to reveal the effect of the found variation on the metabolic pathways of MTB. Partial least squares-discriminant analysis showed a clear differentiation between the two isolates, involving a total of 175 metabolites. Pathway analysis showed that these metabolites are mainly involved in amino sugar and nucleotide sugar metabolism, β-alanine metabolism, sulfur metabolism, and galactose metabolism. The increased ethambutol resistance exhibited by the post-treatment MDR-TB strain could speculatively be linked to the identified genetic variations, which affected the synthesis of a number of metabolites associated with sources of carbon and energy. This may have been the main factor underlying the increased ethambutol resistance of this isolate., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The Latin-American-Mediterranean (LAM) family is among the largest, diverse and intriguing within Mycobacterium tuberculosis. Widespread in some world regions, as justly reflected by its name, LAM remains in the shadow of the Beijing and East-African Indian families in East Asia. Here, we applied evolutionarily robust markers to the spoligotyped collection of 699 M. tuberculosis clinical isolates recovered from tuberculosis (TB) patients in different provinces across China between 2005 and 2013. As a result, only two isolates were assigned to LAM, hence we conclude that this family has a negligible impact on TB transmission in China. Interestingly, these two isolates represented two grand sublineages within LAM: RD115 and RD-Rio/RD174. Our results highlight the great caution to be taken when interpreting spoligotyping profiles with large deleted blocks. Here, three geographically distant Chinese isolates of spoligotype SIT803 were excluded from LAM. This is in clear contrast with described SIT803 isolates of the LAM family in Russia and Georgia (Mokrousov et al., 2014; Niemann et al., 2010). Interestingly, a drug resistant isolate of the Ibero-American LAM RD-Rio sublineage was recovered from TB patient of Tibetan ethnicity, a resident in the Lhasa district in Tibet. An additional in-depth analysis by whole genome sequencing might help to understand the evolutionary history of this isolate and its possible route to the rural setting of the Tibetan highlands., (Copyright © 2014 Elsevier B.V. All rights reserved.)

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., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Mycobacterium tuberculosis Beijing lineage is highly prevalent in Japan. The aim of the present study was to describe the population structure of the Beijing lineage in this country based on 12-, 15-, and 21-loci MIRU-VNTR genotyping schemes. The MIRU-VNTR patterns of Beijing strains from Okinawa, Ryukyu Islands were compared to those recently published from the Osaka-Kobe megalopolis of the main island of Japan, Honshu (Wada et al., 2009). We also compared proportions of "modern/typical" vs. "ancient/atypical" Beijing strains as defined by structure of the NTF locus. Contrarily to the 12-loci Minimum Spanning Tree (MST), the 15- and 21-loci trees allowed the distinction of two groups of strains in Okinawa. A 12-loci MIRU-VNTR pattern (223325173533) corresponding to MIRU international type MIT17 was identified as the most prevalent Beijing genotype in Japan. In the SITVIT2 database, this pattern was found to be disseminated worldwide and corresponded to the most widely distributed Beijing profile in East Asia and former USSR countries. A comparison of 15- and 21-loci MIRU-VNTR patterns showed that two loci (QUB-4156 and Mtub21) were most polymorphic in our study, and could be potential candidates to distinguish between NTF locus based subclassification of Beijing strains. High-resolution VNTR typing using 15- and 21-loci underlined an evolutionarily distinct "ancient/atypical" subpopulation of the Beijing genotype in Okinawa as well as a subgroup of strains closely related to "modern/typical" Beijing strains observed in Osaka/Kobe., (Copyright © 2011 Elsevier B.V. All rights reserved.)

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: http://www.pasteur-guadeloupe.fr:8081/SITVIT_ONLINE., (Copyright © 2012 Elsevier B.V. All rights reserved.)

An interaction of different human alleles and endemic bacterial strains may be clinically manifested as different outcome of the disease in different hosts infected with the same genotype. The primary objective of this study was to investigate this issue in the model of Mycobacterium tuberculosis and human DC-SIGN encoding CD209 promoter SNP (rs4804803) in Russian Siberian population. We sought to find a possible combination of M. tuberculosis lineage and human host allele/genotype correlating with unfavorable outcome of the disease. The 101 paired DNA samples from patients with pulmonary TB (human and M. tuberculosis DNA) were studied by 12-loci MIRU-VNTR typing (M. tuberculosis strains) and CD209 -336 A/G typing (human DNA). Ninety autopsy DNA samples as a source of human and mycobacterial nucleic acids from persons who died from TB were also subjected to the same genotyping procedures. A human control group consisted of 177 healthy individuals. The Beijing genotype was more frequently identified in autopsy versus patient samples, in 70.0% and 51.5%, respectively (χ(2)=6.06, P=0.01). Regarding other M. tuberculosis genetic families, no significant difference in LAM family distribution among patient strains and autopsy samples has been found. In contrast, Ural genotype was significantly less frequently detected in the autopsy samples (χ(2)=6.12, P=0.01). Allelic and genotypic frequencies of the CD209 -336A/G did not differ significantly under global comparison when contrasting controls versus patients versus autopsy samples. However intriguing and contrasting significant associations were found in the male subgroup under M. tuberculosis genotype-stratified comparisons. Firstly, male carriers of -336AA genotype were more frequently infected with Beijing genotype (χ(2)=5.2, P=0.02). Secondly and remarkably, this association was inverted in the autopsy sample: male carriers of -336AA genotype died less frequently due to TB caused by a Beijing rather than a non-Beijing strain (χ(2)=5.37, P=0.02). In conclusion, we hypothesize that although carriers of CD209 -336A allele are more sensitive to infection with a Beijing strain, a combination of human CD209 -336G allele and M. tuberculosis Beijing genotype leads more frequently to the lethal outcome in pulmonary TB male patients in Russian (Caucasian) population., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Genetic factors of human susceptibility to tuberculosis (TB) are multiple and their effect may be ethnic- and age-dependent. TNFR2 encoded by the TNFRSF1B gene is one of the important TNF-α receptors; its polymorphisms were previously suggested as potential markers of host susceptibility to TB. Here, genotyping of three SNPs in TNFRSF1B 3'UTR (rs1061624, rs5030792, rs3397) was performed in Han Chinese pediatric population (229 TB patients and 233 control subjects). rs5030792 was found homozygous (TT genotype) in all studied individuals. The rs3397-T allele was almost equally represented in both gender groups in this study; in particular, it was detected in 33.9% and 35.2% in female cases and controls, respectively (P=0.8). This latter result differs strikingly from an African study where rs3397-T was found in only 12.8 and 16.2% of Ghanaian female cases and controls, respectively (P=0.007 [Möller et al., 2010. Am. J. Respir. Crit. Care. Med. 181, 388-393]). In contrast, rs1061624-A allele, acting recessively, was found to be a possible risk factor for clinical TB in females (P=0.03). The rs1061624 heterozygotes were overdominant in controls versus patients (P=0.015) that warrants further study of their hypothetical advantage in TB. Neither of the common haplotypes was associated with susceptibility to TB. Compared to the published contrasting data on African (7-15%) and European (57%) populations, GTT haplotype was found in an intermediate frequency (26%). Further studies on both adult and pediatric populations in ethnically diverse settings are needed to elucidate the functionality of these 3'UTR SNPs of the TNFR2 gene., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Here, we present results of the first study of the Mycobacterium tuberculosis genotypes circulating in Kyrgyzstan. We focused on the incarcerated population known to be at high-risk for tuberculosis (TB) and with a significant impact on TB incidence in the general population. Beijing genotype was detected in 42 of 56 M. tuberculosis sputum-extracted DNA samples from newly-diagnosed adult pulmonary TB patients. RIF and INH resistance was genotypically detected in 28% and 55% samples; 13 of 15 MDR strains belonged to Beijing genotype. 12-locus MIRU-VNTR typing showed 8 of 56 samples to be mixed cases; 7 of them contained a Beijing strain. MIRU analysis demonstrated a high homogeneity of the studied collection (HGI=0.66) while 28 of 56 strains had a profile 223325153533 corresponding to Beijing/M2 subtype highly prevalent in different Russian settings. Three hypervariable loci, QUB-3232, VNTR-3820 and VNTR-4120, permitted to further subdivide 28 Beijing/M2 strains into 11 subtypes shared by 1 to 9 strains. To conclude, all markers taken together, the penitentiary population of M. tuberculosis in Kyrgyzstan exhibited a strong genetic affinity to Russia and a weak relatedness to East Asia.

The epidemic re-emergence of diphtheria in Russia and the Newly Independent States (NIS) of the former Soviet Union in the 1990s demonstrated the continued threat of this thought to be rare disease. The bacteriophage encoded toxin is a main virulence factor of Corynebacterium diphtheriae, however, an analysis of the first complete genome sequence of C. diphtheriae revealed a recent acquisition of other pathogenicity factors including iron-uptake systems, adhesins and fimbrial proteins as indeed this extracellular pathogen has more possibilities for lateral gene transfer than, e.g., its close relative, mainly intracellular Mycobacterium tuberculosis. C. diphtheriae appears to have a phylogeographical structure mainly represented by area-specific variants whose circulation is under strong influence of human host factors, including health control measures, first of all, vaccination, and social economic conditions. This framework core population structure may be challenged by importation of the endemic and eventually toxigenic strains from new areas thus leading to localized or large epidemics caused directly by imported strains or by bacteriophage-lysogenized indigenous strains converted into toxin production. A feature of C. diphtheriae co-existence with humans is its periodicity: following large epidemic in the 1990s, the present period is marked by increasing heterogeneity of the circulating populations whereas re-emergence of new toxigenic variants along with persistent circulation of invasive non-toxigenic strains appear alarming. To identify and rapidly monitor subtle changes in the genome structure at an infraclonal level during and between epidemics, portable and discriminatory typing methods of C. diphtheriae are still needed. In this view, CRISPRs and minisatellites are promising genomic markers for development of high-resolution typing schemes and databasing of C. diphtheriae.

The Beijing genotype of Mycobacterium tuberculosis has been shown in many settings to be hypervirulent and associated with multi-drug resistance. Its presently global and rapid dissemination makes it an important issue of public health. Here, I present a significantly enlarged update of the MIRU-VNTR global database of the M. tuberculosis Beijing genotype (11 loci). I further attempted to link the observed mycobacterial diversity with relevant events of the known human history. Large water masses have been the most efficient and drastic generators of the genetic divergence between human populations. The same situation appears true also for M. tuberculosis, which general diversity pattern amazingly resembles that of its human host. At the same time, less expected affinities observed between distant populations of M. tuberculosis may reflect hidden patterns of human migrations or yet unknown epidemiological links between distant regions.

We report results of the first study on the molecular basis of drug resistance in Mycobacterium tuberculosis strains currently circulating in Bulgaria. The study panel consisted of 133 (including 37 drug-resistant) isolates recovered from newly diagnosed, adult pulmonary TB patients from different regions of Bulgaria in 2005--2006. Three types of the rpoB mutations were found in 20 of 27 RIF-resistant isolates; rpoB S531L was the most frequent. Eleven (48%) of 23 INH-resistant isolates had katG S315T mutation. inhA -15C > T mutation was detected in one INH-resistant isolate (that also had katG315 mutation) and three INH-susceptible isolates. A mutation in embB306 was found in 7 of 11 EMB-resistant isolates. Comparison with spoligotyping and 24-VNTR locus typing data suggested that emergence and spread of drug-resistant and MDR-TB in Bulgaria are not associated with any specific spoligotype or MIRU-VNTR genotype.