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peptides and tuberculosis

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https://www.readbyqxmd.com/read/28820984/identification-of-m-tuberculosis-antigens-in-the-sera-of-tuberculosis-patients-using-biomimetic-affinity-chromatography-in-conjunction-with-esi-cid-ms-ms
#1
Guorong Ma, Jinting Pan, Jincheng Han, Lina Gao, Shulin Zhang, Rongxiu Li
The profiling of abnormally-expressed proteins in host cells using mass spectrometry (MS) analysis is a classical approach for screening disease-associated biomarkers in clinical diagnosis. However, few pathogen-specific antigens can currently be detected in serum using this proteomic approach, since these are very low-abundant proteins that are easily masked by host high-abundant proteins. Identification of pathogen-specific antigens in the sera of tuberculosis patients is crucial for the clinical diagnosis of this infectious disease, especially in immune-compromised patients...
July 31, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28820946/proteogenomic-investigation-of-strain-variation-in-clinical-mycobacterium-tuberculosis-isolates
#2
Tiaan Heunis, Anzaan Dippenaar, Robin M Warren, Paul D van Helden, Ruben G van der Merwe, Nicolaas C Gey van Pittius, Arnab Pain, Samantha L Sampson, David L Tabb
Mycobacterium tuberculosis consists of a large number of different strains that display unique virulence characteristics. Whole-genome sequencing has revealed substantial genetic diversity among clinical M. tuberculosis isolates, and elucidating the phenotypic variation encoded by this genetic diversity will be of utmost importance to fully understand M. tuberculosis biology and pathogenicity. In this study we integrated whole-genome sequencing and mass spectrometry (GeLC-MS/MS) to reveal strain-specific characteristics in the proteomes of two clinical M...
August 18, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28802403/analytical-evaluation-of-quantiferon-plus-and-quantiferon-gold-in-tube-assays-in-subjects-with-or-without-tuberculosis
#3
E Petruccioli, V Vanini, T Chiacchio, G Cuzzi, D M Cirillo, F Palmieri, G Ippolito, D Goletti
The QuantiFERON-TB Gold Plus (QFT-Plus) represents the new QuantiFERON-TB Gold In-tube (QFT-GIT) to identify latent tuberculosis infection (LTBI). The main differences is the addition of a new tube containing shorter peptides stimulating CD8 T-cells. Aim of this study is to evaluate the accuracy of QFT-Plus compared with QFT-GIT in a cross sectional study of individuals with or without tuberculosis (TB). We enrolled 179 participants: 19 healthy donors, 58 LTBI, 33 cured TB and 69 active TB. QFT-Plus and QFT-GIT were performed...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802397/lysx-gene-is-differentially-expressed-among-mycobacterium-tuberculosis-strains-with-different-levels-of-virulence
#4
Alejandra Montoya-Rosales, Roberta Provvedi, Flor Torres-Juarez, Jose A Enciso-Moreno, Rogelio Hernandez-Pando, Riccardo Manganelli, Bruno Rivas-Santiago
Antimicrobial peptides (AMPs) are mainly produced by epithelial cells and macrophages to eliminate infecting mycobacteria through direct antimicrobial activity and immunomodulation. Indeed, it has been described that this line of defense is essential to control infection. However, Mycobacterium tuberculosis (Mtb) has developed mechanisms to avoid AMPs activity, for instance lysX adds lysine residues to surface phospholipids changing their net charge, leading to the repelling of the AMPs. In the present study, we determined that lysX gene is differentially expressed among Mtb strains...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28776528/humoral-immune-responses-in-mice-immunized-with-region-of-difference-dna-vaccine-constructs-of-pumvc6-and-pumvc7
#5
Shumaila N M Hanif, A S Mustafa
BACKGROUND: We aimed to study the antigen-specific antibody responses in mice immunized with recombinant DNA vaccines constructs of pUMVC6 and pUMVC7, containing RD1 and RD9 genes of Mycobacterium tuberculosis. METHODS: We immunized mice with the parent and recombinant plasmids and sera were collected and tested for antibodies against pure recombinant proteins of RD1 (PE35, PPE68, EsxA, EsxB) and RD9 (EsxV), peptide mixtures of each protein and their individual peptides using enzyme-linked immunosorbent assays...
July 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28759253/differential-recognition-of-mtb-specific-epitopes-as-a-function-of-tuberculosis-disease-history
#6
Thomas J Scriba, Chelsea Carpenter, Sebastian Carrasco Pro, John Sidney, Munyaradzi Musvosvi, Virginie Rozot, Grégory Seumois, Sandy L Rosales, Pandurangan Vijayanand, Delia Goletti, Edward Makgotlho, Willem Hanekom, Mark Hatherill, Bjoern Peters, Alessandro Sette, Cecilia S Lindestam Arlehamn
RATIONALE: Individuals with a history of tuberculosis disease are at elevated risk of disease recurrance. The underlying cause is not known, but one explanation is that previous disease results in less effective immunity against Mycobacterium tuberculosis (Mtb). OBJECTIVE: We hypothesized that the repertoire of Mtb-derived epitopes recognized by T cells from individuals with latent Mtb infection (LTBI) differs as a function of previous diagnosis of active tuberculosis (TB) disease...
July 31, 2017: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/28749951/vitamin-d-deficient-mice-have-more-invasive-urinary-tract-infection
#7
Olof Hertting, Petra Lüthje, Devin Sullivan, Pontus Aspenström, Annelie Brauner
Vitamin D deficiency is a common health problem with consequences not limited to bone and calcium hemostasis. Low levels have also been linked to tuberculosis and other respiratory infections as well as autoimmune diseases. We have previously shown that supplementation with vitamin D can induce the antimicrobial peptide cathelicidin during ex vivo infection of human urinary bladder. In rodents, however, cathelicidin expression is not linked to vitamin D and therefore this vitamin D-related effect fighting bacterial invasion is not relevant...
2017: PloS One
https://www.readbyqxmd.com/read/28739828/mice-bone-marrow-sca-1-cd44-mesenchymal-stem-cells-kill-avirulent-mycobacteria-but-not-mycobacterium-tuberculosis-through-modulation-of-cathelicidin-expression-via-p38-mapk-dependent-pathway
#8
Sumanta Kumar Naik, Avinash Padhi, Geetanjali Ganguli, Srabasti Sengupta, Sanghamitra Pati, Dasarathi Das, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) primarily infects lung macrophages. However, recent study has shown that Mtb also infect and persist in dormant form inside the bone marrow mesenchymal stem cells (BM-MSCs) even after successful antibiotic therapy. However, the mechanism(s) by which Mtb survives in BM-MSCs is still not known. Like macrophages, BM-MSCs do not contain a well-defined endocytic pathway, which is known to play a central role in the clearance of internalized mycobacteria. Here, we studied the fate of virulent and avirulent mycobacteria in Sca-1(+)/CD44(+) BM-MSCs...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28737941/unveiling-the-catalytic-role-of-b-block-histidine-in-the-n-s-acyl-shift-step-of-protein-splicing
#9
Jon I Mujika, Xabier Lopez
Protein splicing is a post-translational modification that involves the excision of a segment denoted as intein and the joining of its two flanking segments. The process is auto-catalytic, making inteins appealing for many applications in biotechnology, bioengineering, or medicine. The canonical mechanism of protein splicing is composed of four sequential steps, and is initialized by an N-S or N-O acyl shift to form a linear ester. It is well established that a histidine, the most conserved amino acid in all inteins catalyzes this initial step, even though its role remains to be understood...
July 24, 2017: Journal of Physical Chemistry. B
https://www.readbyqxmd.com/read/28733429/proteogenomic-analysis-and-discovery-of-immune-antigens-in-mycobacterium-vaccae
#10
Jianhua Zheng, Lihong Chen, Liguo Liu, Haifeng Li, Bo Liu, Dandan Zheng, Tao Liu, Jie Dong, Lilian Sun, Yafang Zhu, Jian Yang, Xiaobing Zhang, Qi Jin
Tuberculosis (TB) is one of the leading causes of death worldwide, especially in developing countries. Neonatal BCG vaccination occurs in various regions, but the level of protection varies in different populations. Recently, Mycobacterium vaccae is found to be an immunomodulating therapeutic agent that could confer a significant level of protection against TB. It is the only vaccine in a phase III trial from WHO to assess its efficacy and safety in preventing TB disease in people with latent TB infection. However, the mechanism of immunotherapy of M...
July 21, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28720735/a-nonredundant-phosphopantetheinyl-transferase-ppta-is-a-novel-antifungal-target-that-directs-secondary-metabolite-siderophore-and-lysine-biosynthesis-in-aspergillus-fumigatus-and-is-critical-for-pathogenicity
#11
Anna Johns, Daniel H Scharf, Fabio Gsaller, Hella Schmidt, Thorsten Heinekamp, Maria Straßburger, Jason D Oliver, Mike Birch, Nicola Beckmann, Katharine S Dobb, Jane Gilsenan, Bharatkumar Rash, Elaine Bignell, Axel A Brakhage, Michael J Bromley
Secondary metabolites are key mediators of virulence for many pathogens. Aspergillus fumigatus produces a vast array of these bioactive molecules, the biosynthesis of which is catalyzed by nonribosomal peptide synthetases (NRPSs) or polyketide synthases (PKSs). Both NRPSs and PKSs harbor carrier domains that are primed for acceptance of secondary metabolic building blocks by a phosphopantetheinyl transferase (P-pant). The A. fumigatus P-pant PptA has been shown to prime the putative NRPS Pes1 in vitro and has an independent role in lysine biosynthesis; however, its role in global secondary metabolism and its impact on virulence has not been described...
July 18, 2017: MBio
https://www.readbyqxmd.com/read/28714174/immunological-properties-and-protective-efficacy-of-a-single-mycobacterial-antigen-displayed-on-polyhydroxybutyrate-beads
#12
Patricia Rubio-Reyes, Natalie A Parlane, Bryce M Buddle, D Neil Wedlock, Bernd H A Rehm
In 2015, there were an estimated 10.4 million new tuberculosis (TB) cases and 1.4 million deaths worldwide. Bacille Calmette-Guérin (BCG), an attenuated strain of Mycobacterium bovis, is the vaccine available against TB, but it is insufficient for global TB control. This study evaluated the immunogenicity of the Mycobacterium tuberculosis antigen Rv1626 in mice while assessing the effect of co-delivering either Cpe30 (immunostimulatory peptide), CS.T3378-395 (promiscuous T helper epitope) or flagellin (TLR5 agonist) or a combination of all three immunostimulatory agents...
July 17, 2017: Microbial Biotechnology
https://www.readbyqxmd.com/read/28700743/polymorphisms-in-the-vitamin-d-receptor-gene-are-associated-with-reduced-rate-of-sputum-culture-conversion-in-multidrug-resistant-tuberculosis-patients-in-south-africa
#13
Matthew J Magee, Yan V Sun, James C M Brust, N Sarita Shah, Yuming Ning, Salim Allana, Angela Campbell, Qin Hui, Koleka Mlisana, Pravi Moodley, Neel R Gandhi
BACKGROUND: Vitamin D modulates the inflammatory and immune response to tuberculosis (TB) and also mediates the induction of the antimicrobial peptide cathelicidin. Deficiency of 25-hydroxyvitamin D and single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene may increase the risk of TB disease and decrease culture conversion rates in drug susceptible TB. Whether these VDR SNPs are found in African populations or impact multidrug-resistant (MDR) TB treatment has not been established...
2017: PloS One
https://www.readbyqxmd.com/read/28699872/in-vitro-synergistic-effects-of-a-short-cationic-peptide-and-clinically-used-antibiotics-against-drug-resistant-isolates-of-brucella-melitensis
#14
Zohreh Mohammadi Azad, Hoda Moravej, Mahdi Fasihi-Ramandi, Faramarz Masjedian, Raziyeh Nazari, Reza Mirnejad, Mehrdad Moosazadeh Moghaddam
PURPOSE: In the last few decades, increasing microbial resistance to common antibiotics has attracted researchers' attention to the development of new classes of antibiotics such as antimicrobial peptides. Accordingly, the aim of the current study was to evaluate antimicrobial effects of the CM11 peptide alone and combined with common antibiotics against drug-resistant isolates of Brucella melitensis. METHODOLOGY: A total of 50 pathogenic samples of B. melitensis were isolated from patients and their antibiotic susceptibility pattern was evaluated by E-test...
July 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28680713/robust-immunoreactivity-of-teenager-sera-against-peptide-19-from-porphyromonas-gingivalis-hsp60
#15
Eun-Young Kwon, Gil Sun Cha, Ji-Young Joo, Ju-Youn Lee, Jeomil Choi
PURPOSE: Epitope spreading is a phenomenon in which distinct subdominant epitopes become major targets of the immune response. Heat shock protein (HSP) 60 from Porphyromonas gingivalis (PgHSP60) and peptide 19 from PgHSP60 (Pep19) are immunodominant epitopes in autoimmune disease patients, including those with periodontitis. It remains unclear whether Pep19 is a dominant epitope in subjects without periodontitis or autoimmune disease. The purpose of this study was to determine the epitope spreading pattern and verify Pep19 as an immunodominant epitope in healthy teenagers using dot immunoblot analysis...
June 2017: Journal of Periodontal & Implant Science
https://www.readbyqxmd.com/read/28676677/hla-e-presents-glycopeptides-from-the-mycobacterium-tuberculosis-protein-mpt32-to-human-cd8-t-cells
#16
Melanie J Harriff, Lisa M Wolfe, Gwendolyn Swarbrick, Megan Null, Meghan E Cansler, Elizabeth T Canfield, Todd Vogt, Katelynne Gardner Toren, Wei Li, Mary Jackson, Deborah A Lewinsohn, Karen M Dobos, David M Lewinsohn
Infection with Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis, remains a global health concern. Both classically and non-classically restricted cytotoxic CD8(+) T cells are important to the control of Mtb infection. We and others have demonstrated that the non-classical MHC I molecule HLA-E can present pathogen-derived peptides to CD8(+) T cells. In this manuscript, we identified the antigen recognized by an HLA-E-restricted CD8(+) T cell clone isolated from an Mtb latently infected individual as a peptide from the Mtb protein, MPT32...
July 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28665555/cd1b-mycolic-acid-tetramers-demonstrate-t-cell-fine-specificity-for-mycobacterial-lipid-tails
#17
Ildiko Van Rhijn, Sarah K Iwany, Peter Fodran, Tan-Yun Cheng, Laurent Gapin, Adriaan J Minnaard, D Branch Moody
Mycobacterium tuberculosis synthesizes a thick cell wall comprised of mycolic acids (MA), which are foreign antigens for human T cells. T-cell clones from multiple donors were used to determine the fine specificity of MA recognition by human αβ T cells. Most CD1-presented lipid antigens contain large hydrophilic head groups comprised of carbohydrates or peptides that dominate patterns of T-cell specificity. MA diverges from the consensus antigen motif in that it lacks a head group. Using multiple forms of natural and synthetic MA and MA-specific T-cells with different T-cell receptors, we found that, unlike antigens with larger head groups, lipid length strongly controlled T-cell responses to MA...
June 30, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28651408/-identification-and-evaluation-of-t-cell-epitopes-of-rv0585c-from-mycobacterium-tuberculosis
#18
X X Wang, X Chen, Y Q Li, T Y Xiao, Y Jiang, M C Li, H C Liu, K L Wan
Objective: To investigate the human T cell epitopes of Mycobacterium (M.) tuberculosis Rv0585c protein antigen and their immunogenicity and provide evidence for the development of specific tuberculosis immune diagnostic techniques and tuberculosis vaccine. Methods: We synthesized peptides from M. tuberculosis Rv0585c protein antigen predicted by TE-predict and IEDB human T cell epitope prediction tool. The cellular immunoreactivity of the predicted peptides was evaluated through ELISpot assay with the peripheral blood monouclear cells (PBMC) of clinical tuberculosis patients...
May 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28636589/identifying-specificity-groups-in-the-t-cell-receptor-repertoire
#19
Jacob Glanville, Huang Huang, Allison Nau, Olivia Hatton, Lisa E Wagar, Florian Rubelt, Xuhuai Ji, Arnold Han, Sheri M Krams, Christina Pettus, Nikhil Haas, Cecilia S Lindestam Arlehamn, Alessandro Sette, Scott D Boyd, Thomas J Scriba, Olivia M Martinez, Mark M Davis
T cell receptor (TCR) sequences are very diverse, with many more possible sequence combinations than T cells in any one individual. Here we define the minimal requirements for TCR antigen specificity, through an analysis of TCR sequences using a panel of peptide and major histocompatibility complex (pMHC)-tetramer-sorted cells and structural data. From this analysis we developed an algorithm that we term GLIPH (grouping of lymphocyte interactions by paratope hotspots) to cluster TCRs with a high probability of sharing specificity owing to both conserved motifs and global similarity of complementarity-determining region 3 (CDR3) sequences...
July 6, 2017: Nature
https://www.readbyqxmd.com/read/28634299/biosynthesis-of-isonitrile-lipopeptides-by-conserved-nonribosomal-peptide-synthetase-gene-clusters-in-actinobacteria
#20
Nicholas C Harris, Michio Sato, Nicolaus A Herman, Frederick Twigg, Wenlong Cai, Joyce Liu, Xuejun Zhu, Jordan Downey, Ryan Khalaf, Joelle Martin, Hiroyuki Koshino, Wenjun Zhang
A putative lipopeptide biosynthetic gene cluster is conserved in many species of Actinobacteria, including Mycobacterium tuberculosis and M. marinum, but the specific function of the encoding proteins has been elusive. Using both in vivo heterologous reconstitution and in vitro biochemical analyses, we have revealed that the five encoding biosynthetic enzymes are capable of synthesizing a family of isonitrile lipopeptides (INLPs) through a thio-template mechanism. The biosynthesis features the generation of isonitrile from a single precursor Gly promoted by a thioesterase and a nonheme iron(II)-dependent oxidase homolog and the acylation of both amino groups of Lys by the same isonitrile acyl chain facilitated by a single condensation domain of a nonribosomal peptide synthetase...
July 3, 2017: Proceedings of the National Academy of Sciences of the United States of America
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