Search

• M.tb adapts to host environments primarily by alterations in its transcriptome. • Remodelling of M.tb cell wall and metabolic pathways was seen in bone TB lesions. • M.tb virulence genes were upregulated in bone lesions and cell line model. • M.tb virulence proteins inhibit osteoblast differentiation, altering bone homeostasis. • Further studies on the role of these proteins in bone TB needed using M.tb mutants. Bone tuberculosis (TB) is the third most common types of extrapulmonary tuberculosis. It is critical to understand mycobacterial adaptive strategies within bone lesions to identify mycobacterial factors that may have role in disease pathogenesis. Whole genome microarray was used to characterize the in-vivo transcriptome of Mycobacterium tuberculosis (M.tb) within bone TB specimens. Mycobacterial virulent proteins were identified by bioinformatic software. An in vitro osteoblast cell line model was used to study the role of these proteins in bone TB pathogenesis. 914 mycobacterial genes were significantly overexpressed and 1688 were repressed in bone TB specimens. Pathway analysis of differentially expressed genes demonstrated a non-replicative and hypometabolic state of M.tb, reinforcement of the mycobacterial cell wall and induction of DNA damage repair responses, suggesting possible survival strategies of M.tb within bone. Bioinformatics mining of microarray data led to identification of five virulence proteins. The genes encoding these proteins were also upregulated in the in vitro MC3T3 osteoblast cell line model of bone TB. Further, exposure of osteoblast cells to two of these virulence proteins (Rv1046c and Rv3663c) significantly inhibited osteoblast differentiation. M.tb alters its transcriptome to establish infection in bone by upregulating certain virulence genes which play a key role in disturbing bone homeostasis. [ABSTRACT FROM AUTHOR]

Summary A major hurdle facing tuberculosis (TB) investigators who want to utilize a rapidly growing body of data from both systems biology approaches and omics technologies is the lack of a standard vocabulary for data annotation and reporting. Lacking a means to readily compare samples from different research groups, a significant quantity of potentially informative data is largely ignored by researchers. To facilitate standardizing data across studies, a simple ontology of TB terms was developed to provide a common vocabulary for annotating data sets. New terminology was developed to address animal models and experimental systems, and existing clinically focused terminology was modified and adapted. This ontology can be used to annotate host TB data in public databases and collaborations, thereby standardizing database searches and allowing researchers to more easily compare results. To demonstrate the utility of a standard TB ontology for host systems biology, a web application was developed to annotate and compare human and animal model gene expression data sets. [ABSTRACT FROM AUTHOR]

Summary The aim of this work was to screen miRNA signatures dysregulated in tuberculosis to improve our understanding of the biological role of miRNAs involved in the disease. Datasets deposited in publically available databases from microarray studies on infectious diseases and malignancies were retrieved, screened, and subjected to further analysis. Effect sizes were combined using the inverse-variance model and between-study heterogeneity was evaluated by the random effects model. 35 miRNAs were differentially expressed (12 up-regulated, 23 down-regulated; p < 0.05) by combining 15 datasets of tuberculosis and other infectious diseases. 15 miRNAs were found to be significantly differentially regulated (7 up-regulated, 8 down-regulated; p < 0.05) by combining 53 datasets of tuberculosis and malignancies. Most of the miRNA signatures identified in this study were found to be involved in immune responses and metabolism. Expression of these miRNA signatures in serum samples from TB subjects (n = 11) as well as healthy controls (n = 10) was examined by TaqMan miRNA array. Taken together, the results revealed differential expression of miRNAs in TB, but available datasets are limited and these miRNA signatures should be validated in future studies. [ABSTRACT FROM AUTHOR]

Summary Tuberculosis (TB) is a communicable disease of major global importance and causes metabolic disorder of the patients. In a previous study, we found that the plasma metabolite profile of TB patients differs from that of healthy control subjects based on nuclear magnetic resonance (NMR) spectroscopy. In order to evaluate the TB specificity of the metabolite profile, a total of 110 patients, including 40 with diabetes, 40 with malignancy, and 30 with community-acquired pneumonia (CAP), assessed by NMR spectroscopy, and compared to those of patients with TB. Based on the orthogonal partial least-squares discriminant analysis (OPLS-DA), the metabolic profiles of these diseases were significant different, as compared to the healthy controls and TB patients, respectively. The score plots of the OPLS-DA model demonstrated that TB was easily distinguishable from diabetes, CAP and malignancy. Plasma levels of ketone bodies, lactate, and pyruvate were increased in TB patient compared to healthy control, but lower than CAP and malignancy. We conclude that the metabolic profiles were TB-specific and reflected MTB infection. Our results strongly support the NMR spectroscopy-based metabolomics could contribute to an improved understanding of disease mechanisms and may offer clues to new TB clinic diagnosis and therapies. [ABSTRACT FROM AUTHOR]

Summary: Clinical reports suggest an association of distinct Mycobacterium tuberculosis strains with CNS disease. We therefore examined CNS dissemination by different laboratory strains (two M. tuberculosis H37Rv, one CDC1551) in a guinea pig aerosol infection model. Although all strains grew exponentially in lungs, with similar bacterial burdens at the time of extrapulmonary dissemination, M. tuberculosis CDC1551 disseminated to the CNS significantly more than the H37Rv strains. No CNS lesions were observed throughout the study, with only a modest cytokine response. These data suggest that M. tuberculosis may have virulence factors that promote CNS dissemination, distinct from those required for pulmonary TB. [Copyright &y& Elsevier]

Objective: This study sought to evaluate the utility of the Global Health Security (GHS) index in predicting the launch of COVID-19 vaccine rollout by Organization for Economic Cooperation and Development (OECD) member countries. Methods : Country-level data on the preparedness to respond to infectious disease threats through vaccination rollout were collected using the GHS index. OECD member countries were rank-ordered based on the percentage of their populations fully vaccinated against COVID-19. Rank-ordering was conducted from the lowest to the highest, with each country assigned a score ranging from 1 to 33. Spearman's rank correlation between the GHS index and the percentage of the population that is fully vaccinated was also performed. Results: Israel, ranked 34th in the world on the GHS index for pandemic preparedness, had the highest percentage of the population that was fully vaccinated against COVID-19 within 2 months of the global vaccine rollout. The Spearman rank correlation coefficient between GHS index and the percentage of population fully vaccinated was -0.1378, with a p-value of 0.43. Conclusion: The findings suggest an absence of correlation between the GHS index rating and the COVID-19 vaccine rollout of OECD countries, indicating that the preparedness of OECD countries for infectious disease threats may not be accurately reflected by the GHS index. [ABSTRACT FROM AUTHOR]