Nuclear magnetic resonance (NMR) spectroscopy is an ideal platform for the metabolic analysis of biofluids due to its high reproducibility, nondestructiveness, nonselectivity in metabolite detection, and the ability to simultaneously quantify multiple classes of metabolites. Tuberculosis (TB) is a chronic wasting inflammatory disease characterized by multisystem involvement, which can cause metabolic derangements in afflicted patients. In this study, we combined multivariate pattern recognition (PR) analytical techniques with 1H NMR spectroscopy to explore the metabolic profile of sera from TB patients. A total of 77 serum samples obtained from patients with TB (n = 38) and healthy controls (n = 39) were investigated. Orthogonal partial least-squares discriminant analysis (OPLS-DA) was capable of distinguishing TB patients from controls and establishing a TB-specific metabolite profile. A total of 17 metabolites differed significantly in concentration between the two groups. Serum samples from TB patients were characterized by increased concentrations of 1-methylhistidine, acetoacetate, acetone, glutamate, glutamine, isoleucine, lactate, lysine, nicotinate, phenylalanine, pyruvate, and tyrosine, accompanied by reduced concentrations of alanine, formate, glycine, glycerolphosphocholine, and low-density lipoproteins relative to control subjects. Our study reveals the metabolic profile of sera from TB patients and indicates that NMR-based methods can distinguish TB patients from healthy controls. NMR-based metabolomics has the potential to be developed into a novel clinical tool for TB diagnosis or therapeutic monitoring and could contribute to an improved understanding of disease mechanisms.Keywords: metabolomics; NMR; serum; systems biology; tuberculosis;

Protein acetylation is a universal post-translational modification which is found in both eukaryotes and prokaryotes. This process is achieved enzymatically by the protein acetyltransferase Pat, and nonenzymatically by metabolic intermediates (e.g., acetyl phosphate) in bacteria. Protein acetylation plays a role in bacterial chemotaxis, metabolism, DNA replication, and other cellular processes. Recently, accumulating evidence has suggested that protein acetylation might be involved in bacterial virulence because a number of bacterial virulence factors are acetylated. In this review, we summarize the progress in understanding bacterial protein acetylation and discuss how it mediates bacterial virulence.

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.

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.

•An MDR strain of M. tb W146 was analyzed by the whole genome sequencing.•Three large genomic deletions were identified in W146.•The missing of furA–katG operon of LGD2 in W146 conferred resistance to isoniazid.Mycobacterium tuberculosis (M.tb) is one of the most prevalent bacterial pathogens in the world. With geographical wide spread and hypervirulence, Beijing/W family is the most successful M.tb lineage. China is a country of high tuberculosis (TB) and high multiple drug-resistant TB (MDR-TB) burden, and the Beijing/W family strains take the largest share of MDR strains. To study the genetic basis of Beijing/W family strains' virulence and drug resistance, we performed the whole genome sequencing of M.tb strain W146, a clinical Beijing/W genotype MDR isolated from Wuxi, Jiangsu province, China. Compared with genome sequence of M.tb strain H37Rv, we found that strain W146 lacks three large fragments and the missing of furA-katG operon confers isoniazid resistance. Besides the missing of furA-katG operon, strain W146 harbored almost all known drug resistance-associated mutations. Comparison analysis of single nucleotide polymorphisms (SNPs) and indels between strain W146 and Beijing/W genotype strains and non-Beijing/W genotype strains revealed that strain W146 possessed some unique mutations, which may be related to drug resistance, transmission and pathogenicity. These findings will help to understand the large sequence polymorphisms (LSPs) and the transmission and drug resistance related genetic characteristics of the Beijing/W genotype of M.tb.