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Due to its rapid spread and association with the numerous outbreaks, the global spread of East Asian lineage of Mycobacterium tuberculosis strains presents a global concern. Although there were many attempts to describe its population structure, no consensus has been reached yet. To define unbiased classification that will facilitate future studies of this lineage, we analyzed the performance and congruence of eight different genotyping schemes based on phylogenetic analysis of 1,398 strains from 32 countries using whole-genome sequencing (WGS) data. We confirm that East Asian lineage comprises two major clades, designated proto-Beijing, which harbors unusual 43-signal spoligoprofile, and Beijing, with well-known spoligoprofile (deleted signals from 1 to 34). We show that different genotyping methods give high consistency results in description of ancient Beijing strains while the classification of modern Beijing strains is significantly divergent due to star-shaped phylogeny. Using WGS data we intersect different studies and for the first time provide balanced classification with well-defined major groups and their genetic markers. Our reconstructed phylogenetic tree can also be used for further analysis of epidemiologically important clusters and their ancestors as well as white spots of unclassified strains, which are prospective areas of research.

Background This study included tuberculosis (TB) patients from high-burden Russian regions of Siberia and Far East. We aimed to assess the impact of the COVID-19 pandemic on the genotypic structure of Mycobacterium tuberculosis population and on epidemiology and clinical course of tuberculosis in TB and TB/COVID-19 coinfected patients. Methods A total of 456 M . tuberculosis isolates were studied and submitted to drug susceptibility testing and genotyping. The modern Beijing genotype and its main Russian epidemic and endemic clusters (B0/W148 and Central Asian/Russian), and ancient Beijing sublineage were detected by PCR assays targeting specific molecular markers. Non-Beijing isolates were spoligotyped and compared to SITVIT2 database. Results More than 80% of strains belonged to the Beijing genotype. Among Beijing strains, genetic clusters B0/W148 and Central-Asian/Russian (94–32) accounted for 94.2% in the pre-pandemic period and 96.6% during the pandemic in the TB group, and 81.5% of TB/COVID-19 group. Moreover, in the pre-pandemic TB group, the ratio of B0/W148 and 94–32 was almost 1:1 (49.7:44.4%), during the pandemic—1.5:1.0 (57.9:38.8%), while in the TB/COVID-19 group, the ratio shifted in favor of the 94–32 cluster and became 1:2 (31.8:65.9%). In TB/COVID patients, the structure of clinical forms shifted from chronic forms (fibrous cavernous TB, tuberculoma) to forms with more active inflammatory and destructive-inflammatory reactions (infiltration, dissemination, cavernous TB). In TB (without COVID-19-coinfection) group, the effectiveness of TB treatment during the pandemic decreased by 20.6% ( p  = 0.002). In the TB/COVID-19 group, the effectiveness of treatment increased, likely due to the predominance of the less frequently MDR Beijing 94–32 cluster in this group. A statistically significant positive correlation was shown between the detection of the 94–32-cluster and the effectiveness of treatment of patients with TB/COVID-19 (Q = 0.56, p  = 0.006). Conclusions Our results are consistent with the reportedly higher ability of Beijing B0/W148 strains (compared to Beijing 94–32) to acquire resistance to anti-TB drugs, their increased virulence and transmissibility. Thus, the seemingly paradoxical, milder clinical course of TB in patients who further developed COVID-19 is explained by a shift in the ratio of M. tuberculosis subtypes due to syndemic interaction between the two epidemics.

Russia is a high-burden area for multidrug-resistant tuberculosis (MDR-TB). Here, we studied the epidemiological situation and drug resistance patterns of Mycobacterium tuberculosis in the Omsk region in Western Siberia. M. tuberculosis isolates (n = 851) were recovered from newly diagnosed TB patients in 2021. The isolates were tested by bacteriological and molecular methods, and long-term epidemiological data were analyzed. The TB incidence dec, this is not variablereased from 93.9 in 2012 to 48.1 in 2021, per 100,000 population, but the primary MDR-TB rate increased from 19.2% to 26.4%. The destructive forms of tuberculosis accounted for 37.8% of all cases, while 35.5% of patients were smear-positive. Of all isolates tested, 55.2% were culture-positive, of which 94.5% were further tested for phenotypic drug resistance and associated mutations. More than half (53.4%) of isolates were drug-resistant, 13.9% were monoresistant and 67.9% were MDR. Among MDR isolates, 40.4% were pre-XDR, and 19.2% were XDR. The spectrum of drug resistance included second-line drugs (new-generation fluoroquinolones, linezolid), which significantly increase the risk of an adverse outcome in patients. In conclusion, our results highlight the critical importance of monitoring drug resistance in circulating M. tuberculosis strains emerging due to ineffective treatment and active transmission.

Human respiratory syncytial virus (HRSV) is a leading cause of acute respiratory infections in children. COVID-19 NPIs significantly suppressed HRSV transmission. This study analyzed six-year epidemiological dynamics of pediatric HRSV infections in Henan Province, China, focusing on NPI suppression effects, the 2023 resurgence, and \"Immune debt\" impact. We retrospectively collected respiratory specimens from 80,920 children with acute respiratory diseases at Henan Children's Hospital (2019-2024). HRSV was detected using RT-qPCR. Positivity rates were analyzed by year, season, and age group. During 2019-2024, HRSV positivity fluctuated markedly: 14.65% (2019), 16.34% (2021), 3.27% (2022 under strict NPIs), 21.47% (2023 post-NPIs), and 6.80% (2024). Interrupted time-series analysis indicated that NPI lifting in 2023 was associated with a significant surge in infection risk (OR = 668.77, 95% CI: 47.03-9509.28). Seasonal patterns shifted substantially, with the characteristic winter peak replaced by an off-season spring outbreak in April 2023 (57.41%). Multivariable logistic regression identified age as the strongest predictor, with infants <1 year having the highest risk (aOR = 9.02, 95% CI: 8.31-9.79) and a 4.91-fold higher positivity rate than school-aged children (22.98% vs. 4.68%; 95% CI: 4.59-5.25; P < 0.001). NPIs dramatically affected HRSV epidemiology. The intense post-suppression rebound strongly supports the \"Immune debt\" theory-accumulation of susceptible children driving resurgence. Establishing year-round, multi-pathogen surveillance systems is crucial for post-pandemic public health challenges.

Background Mycobacterium tuberculosis population in Russia is dominated by the notorious Beijing genotype whose major variants are characterized by contrasting resistance and virulence properties. Here we studied how these strain features could impact the progression of pulmonary tuberculosis (TB) concerning clinical manifestation and lethal outcome. Results The study sample included 548 M . tuberculosis isolates from 548 patients with newly diagnosed pulmonary TB in Omsk, West Siberia, Russia. Strains were subjected to drug susceptibility testing and genotyping to detect lineages, sublineages, and subtypes (within Beijing genotype). The Beijing genotype was detected in 370 (67.5%) of the studied strains. The strongest association with multidrug resistance (MDR) was found for epidemic cluster Beijing B0/W148 (modern sublineage) and two recently discovered MDR clusters 1071–32 and 14717–15 of the ancient Beijing sublineage. The group of patients infected with hypervirulent and highly lethal (in a mouse model) Beijing 14717–15 showed the highest rate of lethal outcome (58.3%) compared to Beijing B0/W148 (31.4%; P  = 0.06), Beijing Central Asian/Russian (29.7%, P  = 0.037), and non-Beijing (15.2%, P  = 0.001). The 14717–15 cluster mostly included isolates from patients with infiltrative but not with fibrous-cavernous and disseminated TB. In contrast, a group infected with low virulent 1071–32-cluster had the highest rate of fibrous-cavernous TB, possibly reflecting the capacity of these strains for prolonged survival and chronicity of the TB process. Conclusions The group of patients infected with hypervirulent and highly lethal in murine model 14717–15 cluster had the highest proportion of the lethal outcome (58.3%) compared to the groups infected with Beijing B0/W148 (31.4%) and non-Beijing (15.2%) isolates. This study carried out in the TB high-burden area highlights that not only drug resistance but also strain virulence should be considered in the implementation of personalized TB treatment.

[This corrects the article DOI: 10.1371/journal.pone.0266837.].

In this study, we aimed to assess the activity of the essential oils from four Bulgarian oil-bearing roses Rosa damascena Mill., R. alba L., R. centifolia L., and R. gallica L., on the reference strain Mycobacterium tuberculosis H37Rv and clinical M. tuberculosis strains of the Beijing and Latin-American Mediterraneum genotypes. The chemical composition of the essential oils was determined by gas chromatography (GC-FID/MS). Minimal inhibitory concentrations (MIC) were determined using the resazurin method. R. alba oil showed the highest inhibitory activity when tested on all strains of different phylogenetic origins with MIC in the range of 0.16–0.31 mg/mL, while R. gallica oil was the least active (MIC 0.62–1.25 mg/mL). The obtained results show heterogeneity of rose oil action on different mycobacterial strains and we hypothesize that the combined level of geraniol and nerol is a key factor that underlies the antimycobacterial action of the rose oils. Strain Beijing 396 was relatively more susceptible to the rose oils probably due to multiple and likely deleterious mutations in its efflux pump genes. Two clinical MDR strains have likely developed during their previous adaptation to anti-TB drugs certain drug tolerance mechanisms that also permitted them to demonstrate intrinsic tolerance to the essential oils. Further research should investigate a possible synergistic action of the new-generation anti-TB drugs and the most promising rose oil extracts on the large panel of different strains.

Background Ural genetic family is a part of the Euro-American lineage of Mycobacterium tuberculosis and is endemic in Northern Eurasia (former Soviet Union [FSU]). These strains were long described as drug susceptible and of low virulence, but recent studies reported an increasing circulation of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) Ural strains. Here, we analyzed all publicly available whole genome sequence data of Ural genotype isolates, in order to elucidate their phylogenomic diversity with a special focus on MDR and potentially epidemic clones. Results A total of 149  M. tuberculosis genomes of Ural isolates from FSU countries were mined from the GMTV database and TB-ARC project. We identified 6002 variable amino acid positions that were assessed for functional significance and used to build ML, NJ trees and for Bayesian TMRCA estimation. Three robust monophyletic clades were identified: Clade A (31 isolates from Russia, Belarus, Moldova), Clade B (52 isolates from Russia), and Clade C (37 isolates from Moldova, 2 from Belarus). Clade C was significantly associated with XDR or pre-XDR status compared to the pooled Clades A and B (33/39 versus 5/83, P  < 0.0001). Time of origin was estimated for Clade A at 77.7–137 years ago and for Clade B at 56.3–99.2 years ago compared to the significantly more recent origin for Clade C. in silico spoligotyping identified signatures specific of the Clade A (spoligotype SIT35), and Clades B and C (both SIT262). Conclusions A genetically compact and evolutionarily young Ural Clade C, likely originated after collapse of the Soviet Union, and reached epidemic proportions in Moldova in the last 20 years. This epidemic pre-XDR clone (mostly rifampin, isoniazid and kanamycin resistant) is characterized by a specific combination of mutations: KatG Ser315Thr, fabG1 -15C > T, RpoB Ser450Leu, RpsL Lys88Arg, eis -12G > A and EmbB Ser297Ala/T > G. Its further dissemination may occur towards both Russia and European Union and should be taken into consideration by health authorities. The identified spoligotyping signatures can serve for rapid preliminary detection and surveillance of the more hazardous pre-XDR associated strains of the Ural family, both in populations from countries of their endemic circulation and migrant communities.

Nigeria ranks 1 st in Africa and 6 th globally with the highest burden of tuberculosis (TB). However, only a relatively few studies have addressed the molecular epidemiology of Mycobacterium tuberculosis in this country. The aim of this work was to analyze the genetic structure of drug-resistant (DR) M . tuberculosis population in the Plateau State (central Nigeria), with the results placed in the broader context of West Africa. The study sample included 67 DR M . tuberculosis isolates, recovered from as many TB patients between November 2015 and January 2016, in the Plateau State. The isolates were subjected to spoligotyping and MIRU-VNTR typing. A total of 20 distinct spoligotypes were obtained, split into 3 clusters (n = 50, 74.6%, 2–33 isolates per cluster) and 17 (25.4%) unique patterns. The Cameroon clade was the largest lineage (62.7%) followed by T (28.3%), LAM (3%), and Haarlem (3%) clades. Upon MIRU-VNTR typing, the isolates produced 31 profiles, i.e. 7 clusters (n = 43, 64.2%, 2–17 isolates per cluster) and 24 singletons. A combined spoligotyping and MIRU-VNTR typing analysis showed 20.9% of the cases clustered and estimated the recent transmission rate at 11.9%. In conclusion, two lineages, namely Cameroon, and T accounted for the majority (91%) of cases. No association was observed between the most prevalent Cameroon lineage and drug resistance, including multidrug resistant (MDR) phenotype, or any of the patient demographic characteristics.

Background This study aimed to evaluate the impact of different Mycobacterium tuberculosis strains on the blood proteinase-inhibitor system and structural changes in the renal parenchyma during the pathogenesis of renal tuberculosis in a rabbit model. Methods Renal tuberculosis was modeled on 60 male Soviet Chinchilla rabbits. The susceptible virulent strain M. tuberculosis H37Rv (Euro-American lineage, group 1) and the low-lethal multidrug-resistant strain 5582 (Beijing Central Asian/Russian cluster; group 2) were injected into the cortex of the lower pole of the left kidney. Blood levels of biomarkers and enzymes were measured at baseline (pre-infection), and 2.5 and 22 weeks after infection. Morphological changes in nephron structures were assessed using 26 indicators at 22 weeks. Whole genome sequencing of M. tuberculosis DNA was performed on the DNBSEQ-G50 MGI platform. Results At 2.5 weeks, group 1 exhibited a significant increase in matrix metalloproteinases (MMP)-1/9 and cystatin C compared to group 2 ( p  = 0.02). After 22 weeks, group 1 showed elevated levels of MMP-9 and ceruloplasmin, alongside reduced levels of tissue inhibitor of metalloproteinases-1 (TIMP-1), cystatin C, and albumin ( p  = 0.02). Group 1 demonstrated a larger area of specific inflammation and less severe fibrotic changes compared to group 2 ( p  = 0.02). Genome of clinical strain 5582 harboured 55 frameshift and 8 stop codon mutations some of which were in genes known to be involved in intracellular survival and pathogenesis. Conclusions In quantitative terms, the structural changes observed in the kidneys of rabbits were inversely related to the virulence of the strains. Specifically, the more virulent strain (H37Rv) induces less pronounced structural changes. Renal tuberculosis induced by H37Rv is characterized by a pronounced imbalance in the MMP/TIMP-1 system, marked by increased MMP-1 and − 9 levels and decreased TIMP-1 levels in the blood. This imbalance is associated with structural kidney damage, including specific and paraspecific changes typical of an immediate hypersensitivity reaction. In contrast, infection with Beijing 5582 maintained a relative balance in the MMP/inhibitor system, with a significant increase in cystatin C and moderately pronounced productive changes in the renal parenchyma, consistent with a delayed hypersensitivity reaction.