Genetic diversity, evolution and drug resistance of Mycobacterium tuberculosis lineage 2.

Mycobacterium tuberculosis causes a chronic infectious disease called tuberculosis. Phylogenetic lineage 2 (L2) of M. tuberculosis, also known as the East Asian lineage, is associated with high virulence, increased transmissibility, and the spread of multidrug-resistant strains. This review article examines the genomic characteristics of the M. tuberculosis genome and M. tuberculosis lineage 2, such as the unique insertion sequence and spoligotype patterns, as well as MIRU-VNTR typing, and SNP-based barcoding. The review describes the geographical distribution of lineage 2 and its history of origin. In addition, the article discusses recent studies on drug resistance and compensatory mechanisms of M. tuberculosis lineage 2 and its impact on the pathogen's transmissibility and virulence. This review article discusses the importance of establishing a unified classification for lineage 2 to ensure consistency in terminology and criteria across different studies and settings.

Candidate protein biomarkers in chronic kidney disease: a proteomics study.

Proteinuria poses a substantial risk for the progression of chronic kidney disease (CKD) and its related complications. Kidneys excrete hundreds of individual proteins, some with a potential impact on CKD progression or as a marker of the disease. However, the available data on specific urinary proteins and their relationship with CKD severity remain limited. Therefore, we aimed to investigate the urinary proteome and its association with kidney function in CKD patients and healthy controls. The proteomic analysis of urine samples showed CKD stage-specific differences in the number of detected proteins and the exponentially modified protein abundance index for total protein (p = 0.007). Notably, specific urinary proteins such as B2MG, FETUA, VTDB, and AMBP exhibited robust negative associations with kidney function in CKD patients compared to controls. Also, A1AG2, CD44, CD59, CERU, KNG1, LV39, OSTP, RNAS1, SH3L3, and UROM proteins showed positive associations with kidney function in the entire cohort, while LV39, A1BG, and CERU consistently displayed positive associations in patients compared to controls. This study suggests that specific urinary proteins, which were found to be negatively or positively associated with the kidney function of CKD patients, can serve as markers of dysfunctional or functional kidneys, respectively.

Draft genome sequence of a multidrug-resistant Mycobacterium tuberculosis clinical isolate, 3184-KZ.

Mycobacterium tuberculosis is an obligate aerobic bacterium that is the causative agent of tuberculosis. Here, we announce the draft genome sequence of multidrug-resistant Mycobacterium tuberculosis clinical isolate, 3184-KZ, from a patient with infiltrative pulmonary tuberculosis from Kazakhstan.

Genomic Characterization of Drug-Resistant Mycobacterium tuberculosis L2/Beijing Isolates from Astana, Kazakhstan.

Kazakhstan ranks among the countries with the highest number of MDR-TB patients per 100,000 population worldwide. The successful transmission of local MDR strains of Mycobacterium tuberculosis (Mtb) poses a significant threat to disease control. In this study, we employed whole-genome sequencing to examine drug resistance, compensatory mutations, population structure, and transmission patterns in a sample of 24 clinical isolates of L2/Beijing Mtb collected in Astana, Kazakhstan between 2021 and 2022. The genotypic prediction of Mtb susceptibility to anti-TB agents was consistent with the phenotypic susceptibility, except for bedaquiline. An analysis of resistance-associated genes characterized most of the isolates as pre-extensively drug-resistant tuberculosis (pre-XDR-TB) (n = 15; 62.5%). The phylogenetic analysis grouped the isolates into four transmission clusters; the dominant cluster was assigned to the "aggressive" Central Asia outbreak (CAO) clade of L2/Beijing (n = 15; 62.5%). Thirteen mutations with putative compensatory effects were observed exclusively in Mtb isolates containing the rpoB S450L mutation. The putative compensatory mutations had a stabilizing effect on RpoABC protein stability and dynamics. The high prevalence of the CAO clade in the population structure of Mtb may explain the rapid spread of MDR-TB in Kazakhstan.

Draft genome sequence of a Fusobacterium nucleatum strain isolated from a patient in Kazakhstan with colorectal cancer.

Fusobacterium nucleatum is an invasive obligate anaerobe found in the oral microbiota and associated with colorectal cancer. Here, we announce the draft genome sequence of Fusobacterium nucleatum strain Fn11kaz from a patient with colorectal cancer in Kazakhstan.

Urinary Protein Profiling for Potential Biomarkers of Chronic Kidney Disease: A Pilot Study.

Proteinuria is a risk factor for chronic kidney disease (CKD) progression and associated complications. However, there is insufficient information on individual protein components in urine and the severity of CKD. We aimed to investigate urinary proteomics and its association with proteinuria and kidney function in early-stage CKD and in healthy individuals. A 24 h urine sample of 42 individuals (21-CKD and 21-healthy individuals) was used for mass spectrometry-based proteomics analysis. An exponentially modified protein abundance index (emPAI) was calculated for each protein. Data were analyzed by Mascot software using the SwissProt database and bioinformatics tools. Overall, 298 unique proteins were identified in the cohort; of them, 250 proteins belong to the control group with median (IQR) emPAI 39.1 (19−53) and 142 proteins belong to the CKD group with median (IQR) emPAI 67.8 (49−117). The level of 24 h proteinuria positively correlated with emPAI (r = 0.390, p = 0.011). The emPAI of some urinary proteomics had close positive (ALBU, ZA2G, IGKC) and negative (OSTP, CD59, UROM, KNG1, RNAS1, CD44, AMBP) correlations (r < 0.419, p < 0.001) with 24 h proteinuria levels. Additionally, a few proteins (VTDB, AACT, A1AG2, VTNC, and CD44) significantly correlated with kidney function. In this proteomics study, several urinary proteins correlated with proteinuria and kidney function. Pathway analysis identified subpathways potentially related to early proteinuric CKD, allowing the design of prospective studies that explore their response to therapy and their relationship to long-term outcomes.

Mitochondrial DNA analysis of ancient sheep from Kazakhstan: evidence for early sheep introduction.

Kazakhstan covers a vast territory, and it has always been a land of nomadic pastoralism, where domesticated horses and sheep were moved by nomadic people across the steppe. Previous reports suggest that sheep breeds from Kazakhstan have an intermediate genetic composition between Asian and European breeds; however, this data appears to be limited. Therefore, we studied the genetic diversity of ancient domestic sheep from two Late Bronze Age settlements, Toksanbai and Kent, located in the Pre-Caspian region of Kazakhstan and central Kazakhstan, respectively. We have applied ZooMS analysis for taxonomic identification of small ruminant remains to select ancient specimens of domestic sheep (Ovis aries). To assign sheep mitochondrial DNA (mtDNA) haplogroups, the single nucleotide polymorphisms (SNPs) from the control region were analyzed by real-time PCR and direct sequencing. Identical distribution of mtDNA haplogroups A (8/14; 57%), B (5/14; 36%), and C (1/14; 7%) was observed in the specimens from Toksanbai (n = 14) and Kent (n = 14). Ovine haplogroup A was predominant in both settlements. Both archeological sites had similar patterns of haplogroup distribution, indicating early sheep introduction into the region. These results are important to gain a better understanding of sheep migrations in the Eurasian steppe and highlight the importance of genomic analysis of earlier local lineages.