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(Mycobacterium AND Tuberculosis)

Fernando Vargas-Romero, Guillermo Mendoza-Hernández, Francisco Suarez-Güemes, Rogelio Hernández-Pando, Mauricio Castañón-Arreola
Mycobacterium bovis is the causative agent of tuberculosis in farms, wildlife and causes sporadic disease in humans. Despite the high similitude in genome sequence between M. bovis strains, some strains like the wild boar 04-303 isolate show a highly virulent phenotype in animal models. Comparative studies will contribute to link protein expression with the virulence phenotype. In vitro, the 04-303 strain was more phagocytized by J774A.1 macrophages in comparison with 444 strain (a cow isolate with the same genotype) and BCG...
October 18, 2016: Microbial Pathogenesis
Giulia Cattaneo, Daniela Ubiali, Enrica Calleri, Marco Rabuffetti, Georg C Höfner, Klaus T Wanner, Marcela C De Moraes, Leonardo K B Martinelli, Diógenes Santiago Santos, Giovanna Speranza, Gabriella Massolini
Mycobacterium tuberculosis (Mtb) purine nucleoside phosphorylase (PNP, EC has been identified as a target for the development of specific inhibitors with potential antimycobacterial activity. We hereby described the development and validation of a new 96-well LC-ESI-MS/MS method to assess the inhibition activity of nucleoside analogues towards MtbPNP and the human PNP (HsPNP). Enzyme activity was determined by monitoring the phosphorolysis of inosine (Ino) to hypoxanthine (Hpx). The enzymatic assay (v = 0...
November 2, 2016: Analytica Chimica Acta
Larry D Teeter, Padmaja Vempaty, Duc T M Nguyen, Jane Tapia, Sharon Sharnprapai, Smita Ghosh, J Steven Kammerer, Roque Miramontes, Wendy A Cronin, Edward A Graviss
BACKGROUND: Tracking the dissemination of specific Mycobacterium tuberculosis (Mtb) strains using genotyped Mtb isolates from tuberculosis patients is a routine public health practice in the United States. The present study proposes a standardized cluster investigation method to identify epidemiologic-linked patients in Mtb genotype clusters. The study also attempts to determine the proportion of epidemiologic-linked patients the proposed method would identify beyond the outcome of the conventional contact investigation...
October 21, 2016: BMC Infectious Diseases
Sarah Thabet, Nada Souissi
The mycobacterial insertion sequence IS6110 proved crucial in deciphering tuberculosis (TB) transmission dynamics. This sequence was also shown to play an important role in the pathogenicity (transmission ability and/or virulence) of Mycobacterium tuberculosis, the main causative agent of TB in humans. In this study, we explored the usefulness of IS6110 and its potential as a phylogenetic/typing marker. We also analyzed the genetic polymorphism and evolutionary trends (selective pressure) of its transposase-encoding open reading frames (ORFs), A and B, using the maximum likelihood method...
October 20, 2016: Molecular Biology Reports
Guoying Deng, Fei Zhang, Shufeng Yang, Jian Kang, Shanshan Sha, Yufang Ma
Tuberculosis remains a global major problem. The immune responses of host against Mycobacterium tuberculosis (M. tuberculosis) are complicated. M. tuberculosis lives mainly within host cells, usually macrophages which constitute the first line of host defense. Mycobacterial proteins, especially cell wall-associated proteins, interact with macrophages of host to regulate the functions and cytokine production. Recent studies indicate that glycoproteins are involved in this process. Here, we investigated the function of Rv0431, a cell wall-associated protein in the M...
October 18, 2016: Microbial Pathogenesis
Jin Kyung Kim, Hye-Mi Lee, Ki-Sun Park, Dong-Min Shin, Tae Sung Kim, Yi Sak Kim, Hyun-Woo Suh, Soo Yeon Kim, In Soo Kim, Jin-Man Kim, Ji-Woong Son, Kyung Mok Sohn, Sung Soo Jung, Chaeuk Chung, Sang-Bae Han, Chul-Su Yang, Eun-Kyeong Jo
Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3'-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages...
October 20, 2016: Autophagy
Gina Leisching, Ray-Dean Pietersen, Carel van Heerden, Paul van Helden, Ian Wiid, Bienyameen Baker
The distinguishing factors that characterize the host response to infection with virulent Mycobacterium tuberculosis (M.tb) are largely confounding. We present an infection study with two genetically closely related M.tb strains that have vastly different pathogenic characteristics. The early host response to infection with these detergent-free cultured strains was analysed through RNAseq in an attempt to provide information on the subtleties which may ultimately contribute to the virulent phenotype. Murine bone marrow derived macrophages (BMDMs) were infected with either a hyper- (R5527) or hypovirulent (R1507) Beijing M...
October 20, 2016: Virulence
Madhukar Pai, Marcel Behr
The identification of individuals with latent tuberculosis infection (LTBI) is useful for both fundamental understanding of the pathogenesis of disease and for clinical and public health interventions (i.e., to prevent progression to disease). Basic research suggests there is a pathogenetic continuum from exposure to infection to disease, and individuals may advance or reverse positions within the spectrum, depending on changes in the host immunity. Unfortunately, there is no diagnostic test that resolves the various stages within the spectrum of Mycobacterium tuberculosis infection...
October 2016: Microbiology Spectrum
Timothy Lahey, C Fordham von Reyn
Tuberculosis infects millions of people worldwide and remains a leading global killer despite widespread neonatal administration of the tuberculosis vaccine, bacillus Calmette-Guérin (BCG). BCG has clear and sustained efficacy, but after 10 years, its efficacy appears to wane, at least in some populations. Fortunately, there are many new tuberculosis vaccines in development today, some in advanced stages of clinical trial testing. Here we review the epidemiological need for tuberculosis vaccination, including evolving standards for administration to at risk individuals in developing countries...
October 2016: Microbiology Spectrum
Racquel Domingo-Gonzalez, Oliver Prince, Andrea Cooper, Shabaana A Khader
Chemokines and cytokines are critical for initiating and coordinating the organized and sequential recruitment and activation of cells into Mycobacterium tuberculosis-infected lungs. Correct mononuclear cellular recruitment and localization are essential to ensure control of bacterial growth without the development of diffuse and damaging granulocytic inflammation. An important block to our understanding of TB pathogenesis lies in dissecting the critical aspects of the cytokine/chemokine interplay in light of the conditional role these molecules play throughout infection and disease development...
October 2016: Microbiology Spectrum
Qiong Jia, Xinling Hu, Dawei Shi, Yan Zhang, Meihao Sun, Jianwei Wang, Kaixia Mi, Guofeng Zhu
The universal stress protein family is a family of stress-induced proteins. Universal stress proteins affect latency and antibiotic resistance in mycobacteria. Here, we showed that Mycobacterium smegmatis overexpressing M. tuberculosis universal stress protein Rv2624c exhibits increased survival in human monocyte THP-1 cells. Transcriptome analysis suggested that Rv2624c affects histidine metabolism, and arginine and proline metabolism. LC-MS/MS analysis showed that Rv2624c affects the abundance of arginine, a modulator of both mycobacteria and infected THP-1 cells...
October 20, 2016: Scientific Reports
K V Shur, M V Zaychikova, N E Mikheecheva, K M Klimina, O B Bekker, S N Zhdanova, O B Ogarkov, V N Danilenko
We report a draft genome sequence of Mycobacterium tuberculosis strain B9741 belonging to Beijing B0/W lineage isolated from a HIV patient from Siberia, Russia. This clinical isolate showed MDR phenotype and resistance to isoniazid, rifampin, streptomycin and pyrazinamide. We analyzed SNPs associated with virulence and resistance. The draft genome sequence and annotation have been deposited at GenBank under the accession NZ_LVJJ00000000.
December 2016: Genomics Data
Nathan J Hare, Ling Y Lee, Ian Loke, Warwick J Britton, Bernadette M Saunders, Morten Thaysen-Andersen
Tuberculosis (TB) remains a prevalent and lethal infectious disease. The glycobiology associated with Mycobacterium tuberculosis infection of front-line alveolar macrophages is still unresolved. Herein, we investigated the regulation of protein N-glycosylation in human macrophages and their secreted microparticles (MPs) used for intercellular communication upon M. tb infection. LC-MS/MS-based proteomics and glycomics were performed to monitor the regulation of glycosylation enzymes and receptors and the N-glycome in in vitro-differentiated macrophages and in isolated MPs upon M...
October 19, 2016: Journal of Proteome Research
Mark R Cronan, Rebecca W Beerman, Allison F Rosenberg, Joseph W Saelens, Matthew G Johnson, Stefan H Oehlers, Dana M Sisk, Kristen L Jurcic Smith, Neil A Medvitz, Sara E Miller, Le A Trinh, Scott E Fraser, John F Madden, Joanne Turner, Jason E Stout, Sunhee Lee, David M Tobin
Mycobacterium tuberculosis infection in humans triggers formation of granulomas, which are tightly organized immune cell aggregates that are the central structure of tuberculosis. Infected and uninfected macrophages interdigitate, assuming an altered, flattened appearance. Although pathologists have described these changes for over a century, the molecular and cellular programs underlying this transition are unclear. Here, using the zebrafish-Mycobacterium marinum model, we found that mycobacterial granuloma formation is accompanied by macrophage induction of canonical epithelial molecules and structures...
October 18, 2016: Immunity
Carl Nathan
In tuberculosis, some macrophages in granulomas assume an epitheloid appearance. Using the Mycobacterium marinum-zebrafish model, Cronan et al. (2016) now show that granuloma macrophages undergo reprograming events involving E-cadherin-dependent formation of epithelial-like cell-cell junctions. Interference with the function of E-cadherin in macrophages disorganized the granulomas and protected the fish, introducing new ideas and questions about macrophage function and granulomatous diseases.
October 18, 2016: Immunity
Jyothi Padiadpu, Priyanka Baloni, Kushi Anand, MohamedHusen Munshi, Chandrani Thakur, Abhilash Mohan, Amit Singh, Nagasuma Chandra
The global mechanisms and associated molecular alterations that occur in drug-resistant mycobacteria are poorly understood. To address this, we obtain genomics data and then construct a genome-scale response network in isoniazid-resistant Mycobacterium smegmatis and apply a network-mining algorithm. Through this, we decipher global alterations in an unbiased manner and identify emergent vulnerabilities in resistant bacilli, of which redox response was prominent. Using phenotypic profiling, we find that resistant bacilli exhibit collateral sensitivity to several compounds that block antioxidant responses...
September 9, 2016: ACS Infectious Diseases
Pooja Gopal, Michelle Yee, Jickky Sarathy, Jian Liang Low, Jansy P Sarathy, Firat Kaya, Véronique Dartois, Martin Gengenbacher, Thomas Dick
Pyrazinamide (PZA) is a critical component of first- and second-line treatments of tuberculosis (TB), yet its mechanism of action largely remains an enigma. We carried out a genetic screen to isolate Mycobacterium bovis BCG mutants resistant to pyrazinoic acid (POA), the bioactive derivative of PZA, followed by whole genome sequencing of 26 POA resistant strains. Rather than finding mutations in the proposed candidate targets fatty acid synthase I and ribosomal protein S1, we found resistance conferring mutations in two pathways: missense mutations in aspartate decarboxylase panD, involved in the synthesis of the essential acyl carrier coenzyme A (CoA), and frameshift mutations in the vitro nonessential polyketide synthase genes mas and ppsA-E, involved in the synthesis of the virulence factor phthiocerol dimycocerosate (PDIM)...
September 9, 2016: ACS Infectious Diseases
J M Greene, P Dash, S Roy, C McMurtrey, W Awad, J S Reed, K B Hammond, S Abdulhaqq, H L Wu, B J Burwitz, B F Roth, D W Morrow, J C Ford, G Xu, J Y Bae, H Crank, A W Legasse, T H Dang, H Y Greenaway, M Kurniawan, M C Gold, M J Harriff, D A Lewinsohn, B S Park, M K Axthelm, J J Stanton, S G Hansen, L J Picker, V Venturi, W Hildebrand, P G Thomas, D M Lewinsohn, E J Adams, J B Sacha
Studies on mucosal-associated invariant T cells (MAITs) in nonhuman primates (NHP), a physiologically relevant model of human immunity, are handicapped due to a lack of macaque MAIT-specific reagents. Here we show that while MR1 ligand-contact residues are conserved between human and multiple NHP species, three T-cell receptor contact-residue mutations in NHP MR1 diminish binding of human MR1 tetramers to macaque MAITs. Construction of naturally loaded macaque MR1 tetramers facilitated identification and characterization of macaque MR1-binding ligands and MAITs, both of which mirrored their human counterparts...
October 19, 2016: Mucosal Immunology
Aditya K Sharma, Divya Arora, Lalit K Singh, Aakriti Gangwal, Andaleeb Sajid, Virginie Molle, Yogendra Singh, Vinay K Nandicoori
Protein phosphatases play vital roles in phosphorylation-mediated cellular signaling. While there are 11 serine/threonine protein kinases in Mycobacterium tuberculosis, only one serine/threonine phosphatase, PstP, has been identified. Although PstP has been biochemically characterized and multiple in vitro substrates identified, its physiological role has not yet been elucidated. In this study we have investigated the impact of PstP on cell growth and survival of the pathogen in the host. Overexpression of PstP led to elongated cells and partially compromised survival...
October 7, 2016: Journal of Biological Chemistry
Simón Menendez-Bravo, Julia Roulet, Martín Sabatini, Santiago Comba, Robert Dunn, Hugo Gramajo, Ana Arabolaza
BACKGROUND: Microbial synthesis of oleochemicals derived from native fatty acid (FA) metabolism has presented significant advances in recent years. Even so, native FA biosynthetic pathways often provide a narrow variety of usually linear hydrocarbons, thus yielding end products with limited structural diversity. To overcome this limitation, we took advantage of a polyketide synthase-based system from Mycobacterium tuberculosis and developed an Escherichia coli platform with the capacity to synthesize multimethyl-branched long-chain esters (MBE) with novel chemical structures...
2016: Biotechnology for Biofuels
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