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peptides and tuberculosis

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https://www.readbyqxmd.com/read/28733429/proteogenomic-analysis-and-discovery-of-immune-antigens-in-mycobacterium-vaccae
#1
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
#2
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
#3
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
#4
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
#5
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 12, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28680713/robust-immunoreactivity-of-teenager-sera-against-peptide-19-from-porphyromonas-gingivalis-hsp60
#6
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
#7
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
#8
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
#9
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
#10
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...
June 21, 2017: Nature
https://www.readbyqxmd.com/read/28634299/biosynthesis-of-isonitrile-lipopeptides-by-conserved-nonribosomal-peptide-synthetase-gene-clusters-in-actinobacteria
#11
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
https://www.readbyqxmd.com/read/28616288/decreased-expression-of-perforin-in-cd8-t-lymphocytes-in-patients-with-mycobacterium-tuberculosis-infection-and-its-potential-value-as-a-marker-for-efficacy-of-treatment
#12
Hongbin Jiang, Huili Gong, Qing Zhang, Jin Gu, Li Liang, Jun Zhang
BACKGROUND: Cytolytic activity against mycobacteria tuberculosis (MTB) within the infected macrophage is a crucial step in the immunity against TB infection, as MTB is an intracellular bacterium. Cytotoxic molecules such as perforin and granzymes produced by cytolytic T cells directly participate in this process. In this study, we evaluated the cytotoxicity function employing flow cytometry analysis of the level of expression of interferon-γ (IFN-γ), perforin and granzyme B in CD8(+) T cells from patients with active pulmonary TB (PTB), stable PTB and healthy controls, and explored whether MTB antigen (MTB Ag)-stimulated cytotoxic molecules would be useful for monitoring responses to anti-TB treatment...
May 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28611371/ohmyungsamycins-promote-antimicrobial-responses-through-autophagy-activation-via-amp-activated-protein-kinase-pathway
#13
Tae Sung Kim, Yern-Hyerk Shin, Hye-Mi Lee, Jin Kyung Kim, Jin Ho Choe, Ji-Chan Jang, Soohyun Um, Hyo Sun Jin, Masaaki Komatsu, Guang-Ho Cha, Han-Jung Chae, Dong-Chan Oh, Eun-Kyeong Jo
The induction of host cell autophagy by various autophagy inducers contributes to the antimicrobial host defense against Mycobacterium tuberculosis (Mtb), a major pathogenic strain that causes human tuberculosis. In this study, we present a role for the newly identified cyclic peptides ohmyungsamycins (OMS) A and B in the antimicrobial responses against Mtb infections by activating autophagy in murine bone marrow-derived macrophages (BMDMs). OMS robustly activated autophagy, which was essentially required for the colocalization of LC3 autophagosomes with bacterial phagosomes and antimicrobial responses against Mtb in BMDMs...
June 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592925/second-generation-multiple-reaction-monitoring-assays-for-enhanced-detection-of-ultra-low-abundance-mycobacterium-tuberculosis-peptides-in-human-serum
#14
Carolina Mehaffy, Karen M Dobos, Payam Nahid, Nicole A Kruh-Garcia
BACKGROUND: Mycobacterium tuberculosis (Mtb) is the causative agent of Tuberculosis (TB), the number one cause of death due to an infectious disease. TB diagnosis is performed by microscopy, culture or PCR amplification of bacterial DNA, all of which require patient sputum or the biopsy of infected tissue. Detection of mycobacterial products in serum, as biomarkers of diagnosis or disease status would provide an improvement over current methods. Due to the low-abundance of mycobacterial products in serum, we have explored exosome enrichment to improve sensitivity...
2017: Clinical Proteomics
https://www.readbyqxmd.com/read/28587935/human-antimicrobial-peptides-in-ocular-surface-defense
#15
REVIEW
Imran Mohammed, Dalia G Said, Harminder S Dua
Sight depends on the passage of light through the transparent cornea and being focused on the fovea. Its exposed position renders it vulnerable to microbial infection. The cornea has developed a wide array of defense mechanisms against infection, of which endogenous antimicrobial peptides (AMPs) are key. AMPs are essentially small molecular weight cationic peptides with a wide range of activity against virus, bacteria, fungi and parasites. Some proteins such as RNases and S100As are also included in this group...
June 3, 2017: Progress in Retinal and Eye Research
https://www.readbyqxmd.com/read/28575388/functional-details-of-the-mycobacterium-tuberculosis-vapbc26-toxin-antitoxin-system-based-on-a-structural-study-insights-into-unique-binding-and-antibiotic-peptides
#16
Sung-Min Kang, Do-Hee Kim, Ki-Young Lee, Sung Jean Park, Hye-Jin Yoon, Sang Jae Lee, Hookang Im, Bong-Jin Lee
Toxin-antitoxin (TA) systems are essential for bacterial persistence under stressful conditions. In particular, Mycobacterium tuberculosis express VapBC TA genes that encode the stable VapC toxin and the labile VapB antitoxin. Under normal conditions, these proteins interact to form a non-toxic TA complex, but the toxin is activated by release from the antitoxin in response to unfavorable conditions. Here, we present the crystal structure of the M. tuberculosis VapBC26 complex and show that the VapC26 toxin contains a pilus retraction protein (PilT) N-terminal (PIN) domain that is essential for ribonuclease activity and that, the VapB26 antitoxin folds into a ribbon-helix-helix DNA-binding motif at the N-terminus...
May 31, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28564390/development-of-an-epitope-panel-for-consistent-identification-of-antigen-specific-t-cells-in-humans
#17
Andreas Fløe, Caroline Løppke, Ole Hilberg, Christian Wejse, Liselotte Brix, Kivin Jacobsen
OBJECTIVE: We aimed to establish a panel of MHC-peptide multimers suitable as a positive control in detection of HLA A*0201 restricted antigen specific T-cells (ASTC) by flow cytometry. MATERIALS AND METHODS: MHC Dextramers were loaded with HLA A*0201 binding peptides from viral antigens and melanoma targets identified from a literature search and in-silico prediction. Peripheral blood mononuclear cells (PBMC) from healthy donors were analysed with the MHC Dextramers using flow cytometry...
May 31, 2017: Immunology
https://www.readbyqxmd.com/read/28536560/comparative-proteomic-analysis-of-mycobacterium-tuberculosis-lineage-7-and-lineage-4-strains-reveals-differentially-abundant-proteins-linked-to-slow-growth-and-virulence
#18
Solomon A Yimer, Alemayehu G Birhanu, Shewit Kalayou, Tahira Riaz, Ephrem D Zegeye, Getachew T Beyene, Carol Holm-Hansen, Gunnstein Norheim, Markos Abebe, Abraham Aseffa, Tone Tønjum
In order to decipher the nature of the slowly growing Mycobacterium tuberculosis (M.tuberculosis) lineage 7, the differentially abundant proteins in strains of M. tuberculosis lineage 7 and lineage 4 were defined. Comparative proteomic analysis by mass spectrometry was employed to identify, quantitate and compare the protein profiles of strains from the two M. tuberculosis lineages. Label-free peptide quantification of whole cells from M. tuberculosis lineage 7 and 4 yielded the identification of 2825 and 2541 proteins, respectively...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28530443/association-of-single-nucleotide-polymorphism-in-the-hepcidin-promoter-gene-with-susceptibility-to-extrapulmonary-tuberculosis
#19
Li Liang, Huijuan Liu, Jun Yue, Li-Rong Liu, Min Han, Liu-Lin Luo, Yan-Lin Zhao, Heping Xiao
BACKGROUND: Hepcidin is a 25-amino acid peptide produced by the liver in response to inflammation and iron overload. It is encoded by the hepcidin antimicrobial peptide (HAMP) gene and plays a key role in innate immunity. Previous studies have reported that a -582 A>G polymorphism in the HAMP promoter (HAMP-P) affects hepcidin expression, causing susceptibility to various bacterial and viral pathogens. However, it is not known whether the HAMP-P -582 A>G polymorphism is associated with tuberculosis (TB) susceptibility...
June 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28496439/bortezomib-warhead-switch-confers-dual-activity-against-mycobacterial-caseinolytic-protease-and-proteasome-and-selectivity-against-human-proteasome
#20
Wilfried Moreira, Sridhar Santhanakrishnan, Brian W Dymock, Thomas Dick
Mycobacteria harbor two main degradative proteolytic machineries, the caseinolytic protease ClpP1P2 and a proteasome. We recently showed that Bortezomib inhibits ClpP1P2 and exhibits whole cell activity against Mycobacterium tuberculosis. Bortezomib, a dipeptide with a boronic acid warhead, is a human proteasome inhibitor approved for cancer therapy. The boronic acid warhead of the compound has been shown to drive potency against both the human proteasome and ClpP1P2 protease. Selectivity for the bacterial ClpP1P2 protease over the human proteasome is lacking but needs to be achieved to move this new anti-tuberculosis lead forward...
2017: Frontiers in Microbiology
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