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https://www.readbyqxmd.com/read/30543940/the-dynamic-region-of-the-peptidoglycan-synthase-gene-rv0050-induces-the-growth-rate-and-morphologic-heterogeneity-in-mycobacteria
#1
Beilan Gao, Jie Wang, Jing Huang, Xiaochen Huang, Wei Sha, Lianhua Qin
Mycobacterium tuberculosis (MTB) infections rely on continued growth and division. Despite the substantial global burden of tuberculosis, the underlying mechanism governing growth is incompletely understood. Bifunctional penicillin-binding protein (PBP1), encoded by Rv0050 (ponA1) of MTB, is a key peptidoglycan synthase and plays a central role in mycobacterial growth and division by its interaction with Rpf-interacting protein A (RipA, peptidoglycan endopeptidase). Our previous work suggested that the hyper-variable proline repeats are located at the N end of PBP1...
December 10, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/30543804/development-of-high-throughput-screening-methods-for-inhibitors-of-clpc1p1p2-from-mycobacteria-tuberculosis
#2
Hugo Fraga, Beatriz Rodriguez, Ana Bardera, Concha Cid, Tatos Akopian, Olga Kandror, Annie Park, Gonzalo Colmenarejo, Joel Lelievre, Alfred Goldberg
Tuberculosis affects about 100 million people worldwide and causes nearly 2 million deaths annually. It has been estimated that one third of all humans is infected with latent Mycobacterium tuberculosis (Mtb). Moreover, Mtb has become increasingly resistant to available antibiotics. Consequently, it is important to identify and characterize new therapeutic targets in Mtb and to synthesize selective inhibitors. ClpP1, ClpP2 and their associated regulatory ATPases, ClpX and ClpC1 are required for the growth of Mtb and for its virulence during murine infection and are highly attractive drug targets, especially since they are not present in the cytosol of mammalian cells, and they differ markedly from the mitochondrial ClpP complex...
December 10, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/30514512/comparative-evaluation-of-xpert-mtb-rif-assay-with-multiplex-polymerase-chain-reaction-for-the-diagnosis-of-tuberculous-meningitis
#3
Kusum Sharma, Megha Sharma, Lokesh Chaudhary, Manish Modi, Manoj Goyal, Navneet Sharma, Aman Sharma, Anumiti Jain, Deba Prasad Dhibar, Kajal Jain, Niranjan Khandelwal, Pallab Ray, Vivel Lal, Max Salfinger
BACKGROUND: Rapid and specific diagnosis of tuberculous meningitis (TBM) is of paramount importance to decrease morbidity and mortality. Therefore, the present study was undertaken to compare the efficacy of Xpert MTB/RIF assay (GXpert) and multiplex PCR (MPCR) using three targets (IS6110, MPB64 and protein B) for diagnosing tuberculous meningitis. METHODS: GXpert and MPCR were performed on cerebrospinal fluid samples of 225 patients out of which 80 were culture-positive confirmed cases of TBM, 100 were 'suspected' cases of TBM and 45 were non-TBM controls...
December 2018: Tuberculosis
https://www.readbyqxmd.com/read/30498982/epitope-and-affinity-determination-of-recombinant-mycobacterium-tuberculosis-ag85b-antigen-towards-anti-ag85-antibodies-using-proteolytic-affinity-mass-spectrometry-and-biosensor-analysis
#4
Francesca Rinaldi, Loredana Lupu, Hendrik Rusche, Zdeněk Kukačka, Sara Tengattini, Roberta Bernardini, Luciano Piubelli, Teodora Bavaro, Stefan Maeser, Loredano Pollegioni, Enrica Calleri, Michael Przybylski, Caterina Temporini
Tuberculosis (TB) is the first cause of death from infectious diseases worldwide. Only a single anti-TB vaccine is currently available for clinical use, but its efficacy is not achieved with certainty. The aim of this work is to provide a basis for the rational design of a neo-glycoconjugate vaccine against TB. Structural characterization of recombinant antigenic proteins from Mycobacterium tuberculosis (MTB) Ag85B (rAg85B, variants, and semi-synthetic glycoconjugates) was initially carried out. Identification of antibody epitope analyses by proteolytic affinity-mass spectrometry and surface plasmon resonance (SPR) biosensor analyses were performed in order to qualitatively identify and quantitatively characterize interaction structures of the antigens with antibodies from different sources...
November 29, 2018: Analytical and Bioanalytical Chemistry
https://www.readbyqxmd.com/read/30484328/immune-responses-elicited-by-the-recombinant-erp-hspr-lppx-mmaa4-and-ompa-proteins-from-mycobacterium-tuberculosis-in-mice
#5
Sezer Okay, Rukiye Çetin, Fatih Karabulut, Cennet Doğan, Süheyla Sürücüoğlu, Aslıhan Kurt Kızıldoğan
Immunogenic potency of the recombinant Erp, HspR, LppX, MmaA4, and OmpA proteins from Mycobacterium tuberculosis (MTB), formulated with Montanide ISA 720 VG adjuvant, was evaluated in BALB/c mice for the first time in this study. The five vaccine formulations, adjuvant, and BCG vaccine were subcutaneously injected into mice, and the sera were collected at days 0, 15, 30, 41, and 66. The humoral and cellular immune responses against vaccine formulations were determined by measuring serum IgG and serum interferon-gamma (IFN-γ) and interleukin-12 (IL-12) levels, respectively...
November 28, 2018: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/30481017/insights-into-the-mechanisms-of-pyrazinamide-resistance-of-three-pyrazinamidase-mutants-n11k-p69t-and-d126n
#6
Muhammad Junaid, Muhammad Tahir Khan, Shaukat Iqbal Malik, Dong-Qing Wei
In an effort to discover the mechanism of resistance offered by Mycobacterium tuberculosis (Mtb) toward the pyrazinamide (PZA) drug, an extensive molecular dynamics strategy was employed. PZA is a first-line prodrug that effectively cuts the therapy time by 33% (from 9 to 6 months). Pyrazinamidase enzyme (PZase), encoded by the pncA gene, is responsible for the activation of prodrug PZA into pyrazinoic acid (POA). POA is toxic and potently inhibit the growth of latent Mtb even at low pH. PZA resistance is caused by three genes pncA, rpsA, and panD...
November 27, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/30478834/expression-and-regulatory-networks-of-mycobacterium-tuberculosis-pe-ppe-family-antigens
#7
REVIEW
Wu Li, Wanyan Deng, Jianping Xie
PE/PPE family antigens are distributed mainly in pathogenic mycobacteria and serve as potential antituberculosis (TB) vaccine components. Some PE/PPE family antigens can regulate the host innate immune response, interfere with macrophage activation and phagolysosome fusion, and serve as major sources of antigenic variation. PE/PPE antigens have been associated with mycobacteria pathogenesis; pe/ppe genes are mainly found in pathogenic mycobacteria and are differentially expressed between Mtb and Mycobacterium bovis...
November 27, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/30478257/iron-homeostasis-in-mycobacterium-tuberculosis-is-essential-for-persistence
#8
Manitosh Pandey, Sakshi Talwar, Sutapa Bose, Amit Kumar Pandey
Tuberculosis, caused by the obligate intracellular pathogen Mycobacterium tuberculosis (Mtb), is responsible for 2-3 million deaths annually worldwide. Intracellular adaptability, which is critical for long-term persistence, requires the pathogen to neutralize host-mediated insults. The iron-sulphur (Fe-S) cofactor is essential for many enzymes critical for such 'adaptation'. The Mtb genome harbors only one putative iron-sulphur cluster (ISC) operon (rv1460-66) predicted to be involved in the generation of the Fe-S cofactor...
November 26, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30477360/advances-and-challenges-in-drug-design-against-tuberculosis-application-of-in-silico-approaches
#9
Alexey Aleksandrov, Hannu Myllykallio
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) remains the deadliest infectious disease in the world with one-third of the world's population thought to be infected. Over the years, TB mortality rate has been largely reduced; however, this progress has been threatened by the increasing appearance of multidrug-resistant Mtb. Considerable recent efforts have been undertaken to develop new generation antituberculosis drugs. Many of these attempts have relied on in silico approaches, which have emerged recently as powerful tools complementary to biochemical attempts...
November 26, 2018: Expert Opinion on Drug Discovery
https://www.readbyqxmd.com/read/30476068/toxin-antitoxin-systems-shows-variability-among-mycobacterium-tuberculosis-lineages
#10
J S Solano-Gutierrez, C Pino, J Robledo
The Toxin-Antitoxin (TA) systems are operons involved in the formation of persistent cells and in stress situations in microorganism. TAs are widely distributed in Mycobacterium tuberculosis (MTB). The objective of this study was to determine the distribution and variability of protein sequences of TA systems in seven MTB lineages. Protein prediction on 73 genomes of different lineage was made using Prodigal, and profile hidden Markov models (PHMMs) of 225 reference TA proteins were constructed with HMMER. A homology search was made comparing the predicted proteins to PHMMs...
November 26, 2018: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/30475863/ppe17-rv1168c-protein-of-mycobacterium-tuberculosis-detects-individuals-with-latent-tb-infection
#11
Philip Raj Abraham, Kamakshi Prudhula Devalraju, Vishwanath Jha, Vijaya Lakshmi Valluri, Sangita Mukhopadhyay
Latent tuberculosis infection (LTBI) is a clinically distinct category of Mycobacterium tuberculosis (Mtb) infection that needs to be diagnosed at the initial stage. We have reported earlier that one of the Mtb proline-proline-glutamic acid (PPE) proteins, PPE17 (Rv1168c) is associated with stronger B-cell and T-cell responses and could be used to diagnose different clinical categories of active TB patients with higher specificity and sensitivity than PPD and ESAT-6. Based on these observations we further tested the potential of PPE17 for the diagnosis of LTBI...
2018: PloS One
https://www.readbyqxmd.com/read/30471865/ppe65-of-m-tuberculosis-regulate-pro-inflammatory-signalling-through-lrr-domains-of-toll-like-receptor-2
#12
Rahila Qureshi, Nagender Rao Rameshwaram, Madhu Babu Battu, Sangita Mukhopadhyay
Our understanding of the PE/PPE family of proteins in M. tuberculosis (Mtb) pathogenesis is still evolving and their critical roles in the host immunomodulation are still in the discovery process. Earlier studies from our group have shown that TLR2-LRR domain plays an important role in regulating cytokine signalling by PPE proteins. The importance of TLR2-LRR domain 16-20 in the regulation of PPE17-induced pro-inflammatory signalling has been established recently. However, it is yet to find whether other PPE protein also targets the TLR2-LRR 16-20 domain for induction of pro-inflammatory responses...
November 21, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/30466358/molecular-dynamics-analysis-of-the-effects-of-gtp-gdp-and-benzimidazole-derivative-on-structural-dynamics-of-a-cell-division-protein-ftsz-from-mycobacterium-tuberculosis
#13
Supriya Hakeem, Inderpal Singh, Preeti Sharma, Anshul Uppal, Yugal Khajuria, Vijeshwar Verma, Vladimir N Uversky, Ratna Chandra
The prevailing multi-drug resistance in Mycobacterium tuberculosis continues to remain one of the main challenges to combat tuberculosis. Hence, it becomes imperative to focus on novel drug targets. Filamenting temperature-sensitive mutant Z (FtsZ) is an essential cell division protein, a eukaryotic tubulin homologue and a promising drug target. During cytokinesis, FtsZ polymerises in the presence of GTP to form Z-ring and recruits other proteins at this site that eventually lead to the formation of daughter cells...
November 22, 2018: Journal of Biomolecular Structure & Dynamics
https://www.readbyqxmd.com/read/30456576/ethambutol-targets-the-glutamate-racemase-of-mycobacterium-tuberculosis-an-enzyme-involved-in-peptidoglycan-biosynthesis
#14
Alka Pawar, Prakash Jha, Chandrika Konwar, Uma Chaudhry, Madhu Chopra, Daman Saluja
Increasing drug resistance in pathogens including Mycobacterium tuberculosis (MTB) has been ascribed to mutations in the known target genes. However, many of these drugs have multiple targets; some of which have not been identified so far. Understanding the mechanism of action of these drugs holds a great promise in better management of disease especially by drug-resistant strains. In this study, we report glutamate racemase (MurI), a crucial enzyme of phase I peptidoglycan (PG) biosynthesis pathway of MTB, as an additional target of ethambutol (EMB)...
November 19, 2018: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/30455201/ppe37-is-essential-for-mycobacterium-tuberculosis-heme-iron-acquisition-hia-and-a-defective-ppe37-in-mycobacterium-bovis-bcg-prevents-hia
#15
Michael V Tullius, Susana Nava, Marcus A Horwitz
Mycobacterium tuberculosis (Mtb), one of the world's leading causes of death, must acquire nutrients, such as iron, from the host to multiply and cause disease. Iron is an essential metal and Mtb possesses two different systems to acquire iron from its environment: Siderophore-Mediated Iron Acquisition (SMIA) and Heme-Iron Acquisition (HIA), involving uptake and degradation of heme to release ferrous iron. We have discovered that Mycobacterium bovis BCG, the tuberculosis vaccine strain, is severely deficient in HIA, and exploited this phenotypic difference between BCG and Mtb to identify genes involved in HIA by complementing BCG's defect with a fosmid library...
November 19, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/30440886/in-silico-model-of-vitamin-d-3-dependent-nadph-oxidase-complex-activation-during-mycobacterium-infection
#16
Maya Gough, Elebeoba May
Mycobacterium tuberculosis (Mtb) is a highly infectious aerosolizable bacterium, which causes upward of 1.5 million deaths per year. Alveolar macrophages, the primary defense cell of the lung, are the preferred host cell of this intracellular bacterium. Vitamin D3 is a known transcription factor, modulating the transcription of pro- and anti-inflammatory cytokines and immunologically relevant proteins. In a vitamin D3 deficient host, the immune systems response to infection is greatly impaired. We used a quantitative systems biology approach to model the impact of long-term vitamin D3 deficiency on macrophage effector response...
July 2018: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/30409901/the-ribosomal-maturation-factor-p-from-mycobacterium-smegmatis-facilitates-the-ribosomal-biogenesis-by-binding-to-the-small-ribosomal-protein-s12
#17
Tinyi Chu, Xing Weng, Carmen Oi Kwan Law, Hoi-Kuan Kong, Jeffrey Lau, Sheila Li, Hoa Quynh Pham, Rui Wang, Liang Zhang, Richard Y T Kao, Kwok-Fai Lau, Jacky Chi Ki Ngo, Terrence Chi Kong Lau
The ribosomal maturation factor P RimP is a highly conserved protein in bacteria and has been shown to be important in ribosomal assembly in Escherichia coli ( E coli ). Because of its central importance in bacterial metabolism, RimP represents a good potential target for drug design to combat human pathogens such as Mycobacterium tuberculosis ( Mtb ). However, to date the only RimP structure available is the NMR structure of the ortholog in another bacterial pathogen Streptococcus pneumoniae Here, we report a 2...
November 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/30405554/understanding-the-biomineralization-role-of-magnetite-interacting-components-mics-from-magnetotactic-bacteria
#18
Hila Nudelman, Yi-Zong Lee, Yi-Lin Hung, Sofiya Kolusheva, Alexander Upcher, Yi-Chen Chen, Jih-Ying Chen, Shih-Che Sue, Raz Zarivach
Biomineralization is a process that takes place in all domains of life and which usually helps organisms to harden soft tissues by creating inorganic structures that facilitate their biological functions. It was shown that biominerals are under tight biological control via proteins that are involved in nucleation initiation and/or which act as structural skeletons. Magnetotactic bacteria (MTB) use iron biomineralization to create nano-magnetic particles in a specialized organelle, the magnetosome, to align to the geomagnetic field...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30366125/ppe11-of-mycobacterium-tuberculosis-can-alter-host-inflammatory-response-and-trigger-cell-death
#19
Xuan Peng, Tao Luo, Xiaoqian Zhai, Chunxi Zhang, Jing Suo, Pengjiao Ma, Chuhan Wang, Lang Bao
Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains a serious global health problem. The PE/PPE family, featuring unique sequences, structures and expression in Mtb, is reported to interfere with the macrophage response to the pathogen and facilitate its infection. PPE11 (Rv0453) existed in pathogenic mycobacteria and was persistently expressed in the infected guinea pig lungs. However, the role it played in the pathogenesis remains unclear. Here, to investigate the interaction and potential mechanism of PPE11 between pathogens and hosts, we heterologously expressed PPE11 in non-pathogenic, rapidly growing Mycobacterium smegmatis strains...
October 23, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/30352198/a-novel-aptamer-based-test-for-the-rapid-and-accurate-diagnosis-of-pleural-tuberculosis
#20
Pooja Kumari, Surabhi Lavania, Shaifali Tyagi, Abhijeet Dhiman, Deepak Rath, Divya Anthwal, Rakesh Kumar Gupta, Neera Sharma, A K Gadpayle, R S Taneja, Lokesh Sharma, Yusra Ahmad, Tarun Kumar Sharma, Sagarika Haldar, Jaya Sivaswami Tyagi
Pleural tuberculosis (pTB) is diagnosed by using a composite reference standard (CRS) since microbiological methods are grossly inadequate and an accurate diagnostic test remains an unmet need. The present study aimed to evaluate the utility of Mycobacterium tuberculosis (Mtb) antigen and DNA-based tests for pTB diagnosis. Patients were classified as 'Definite TB', 'Probable TB' and 'Non-TB' disease according to the CRS. We assessed the performance of in-house antigen detection assays, namely antibody-based Enzyme-Linked ImmunoSorbent Assay (ELISA) and aptamer-based Aptamer-Linked Immobilized Sorbent Assay (ALISA), targeting Mtb HspX protein and DNA-based tests namely, Xpert MTB/RIF and in-house devR-qPCR...
January 1, 2019: Analytical Biochemistry
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