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peptides and tuberculosis

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https://www.readbyqxmd.com/read/28636589/identifying-specificity-groups-in-the-t-cell-receptor-repertoire
#1
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
#2
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...
June 20, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28495884/the-uniqueness-of-subunit-%C3%AE-of-mycobacterial-f-atp-synthases-an-evolutionary-variant-for-niche-adaptation
#12
Priya Ragunathan, Hendrik Sielaff, Lavanya Sundararaman, Goran Biuković, Malathy Sony Subramanian Manimekalai, Dhirendra Singh, Subhashri Kundu, Thorsten Wohland, Wayne Frasch, Thomas Dick, Gerhard Grüber
The F1FO ATP (F-ATP) synthase is essential for growth of Mycobacterium tuberculosis, the causative agent of tuberculosis (TB). In addition to their synthase function most F-ATP synthases possess an ATP-hydrolase activity, which is coupled to proton-pumping activity. However, the mycobacterial enzyme lacks this reverse activity, but the reason for this deficiency is unclear. Here, we report that a Mycobacterium-specific, 36 amino acid long C-terminal domain in the nucleotide-binding subunit α (Mtα) of F-ATP synthase suppresses its ATPase activity and determined the mechanism of suppression...
May 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28481113/hydrogen-deuterium-exchange-mass-spectrometry-reveals-mechanistic-details-of-activation-of-nucleoside-diphosphate-kinases-by-oligomerization
#13
Alain Dautant, Philippe Meyer, Florian Georgescauld
Most oligomeric proteins become active only after assembly, but why oligomerization is required to support function is not well understood. Here, we address this question using the wild type (WT) and a destabilized mutant (D93N) of the hexameric nucleoside diphosphate kinase from the pathogen Mycobacterium tuberculosis (Mt-NDPK). The conformational dynamics and oligomeric states of each were analyzed during unfolding and/or folding by hydrogen/deuterium exchange mass spectrometry (HDX-MS) at peptide resolution and by additional biochemical techniques...
May 17, 2017: Biochemistry
https://www.readbyqxmd.com/read/28475642/mhc-ib-molecule-qa-1-presents-mycobacterium-tuberculosis-peptide-antigens-to-cd8-t-cells-and-contributes-to-protection-against-infection
#14
Yao Bian, Shaobin Shang, Sarah Siddiqui, Jie Zhao, Simone A Joosten, Tom H M Ottenhoff, Harvey Cantor, Chyung-Ru Wang
A number of nonclassical MHC Ib molecules recognizing distinct microbial antigens have been implicated in the immune response to Mycobacterium tuberculosis (Mtb). HLA-E has been identified to present numerous Mtb peptides to CD8+ T cells, with multiple HLA-E-restricted cytotoxic T lymphocyte (CTL) and regulatory T cell lines isolated from patients with active and latent tuberculosis (TB). In other disease models, HLA-E and its mouse homolog Qa-1 can act as antigen presenting molecules as well as regulators of the immune response...
May 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28446822/anti-mycobacterium-activity-of-microbial-peptides-in-a-silkworm-infection-model-with-mycobacterium-smegmatis
#15
Akiho Yagi, Ryuji Uchida, Hiroshi Hamamoto, Kazuhisa Sekimizu, Ken-Ichi Kimura, Hiroshi Tomoda
An in vivo-mimic silkworm infection model with Mycobacterium smegmatis was established. When silkworms were raised at 37 °C following an injection of M. smegmatis cells (1.25 × 10(7) CFU larva(-1) g(-1)) into the silkworm hemolymph, they died within 48 h. Under these conditions, four microbial peptides with anti-M. smegmatis activity, lariatin A, calpinactam, lysocin E and propeptin, exerted therapeutic effects in a dose-dependent manner, and these are also clinically used agents that are active against Mycobacterium tuberculosis...
May 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28423019/design-synthesis-and-structure-activity-relationship-study-of-wollamide-b-a-new-potential-anti-tb-agent
#16
Henok Asfaw, Katja Laqua, Anna Maria Walkowska, Fraser Cunningham, Maria Santos Martinez-Martinez, Juan Carlos Cuevas-Zurita, Lluís Ballell-Pages, Peter Imming
Wollamide B is a cationic antimycobacterial cyclohexapeptide that exhibits activity against Mycobacterium bovis (M. bovis) (IC50 of 3.1 μM). Aiming to define its structural activity relationship (SAR), optimizing potency and pharmacokinetic properties, libraries of analogues were synthesized following a standard Fmoc-based solid phase peptide synthesis approach. The antimycobacterial activities of wollamide B and all the synthesized analogues were tested against Mycobacterium tuberculosis (Mtb) H37Rv. Parallely, in vitro drug metabolism and pharmacokinetic (ADME) profiling was done for the synthesized compounds to evaluate their drug likeness...
2017: PloS One
https://www.readbyqxmd.com/read/28419973/antibacterial-antifungal-and-antimycobacterial-compounds-from-cyanobacteria
#17
REVIEW
Shasank S Swain, Sudhir K Paidesetty, Rabindra N Padhy
Infections from multidrug resistant (MDR) pathogenic bacteria, fungi and Mycobacterium tuberculosis remain progressively intractable. The search of effective antimicrobials from other possible non-conventional sources against MDR pathogenic bacteria, fungi and mycobacteria is call of the day. This review considers 121 cyanobacterial compounds or cyano-compounds with antimicrobial activities. Chemical structures of cyano-compounds were retrieved from ChemSpider and PubChem databases and were visualized by the software ChemDraw Ultra...
June 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28401156/computational-identification-and-characterization-of-a-promiscuous-t-cell-epitope-on-the-extracellular-protein-85b-of-mycobacterium-spp-for-peptide-based-subunit-vaccine-design
#18
Md Saddam Hossain, Abul Kalam Azad, Parveen Afroz Chowdhury, Mamoru Wakayama
Tuberculosis (TB) is a reemerging disease that remains as a leading cause of morbidity and mortality in humans. To identify and characterize a T-cell epitope suitable for vaccine design, we have utilized the Vaxign server to assess all antigenic proteins of Mycobacterium spp. recorded to date in the Protegen database. We found that the extracellular protein 85B displayed the most robust antigenicity among the proteins identified. Computational tools for identifying T-cell epitopes predicted an epitope, 181-QQFIYAGSLSALLDP-195, that could bind to at least 13 major histocompatibility complexes, revealing the promiscuous nature of the epitope...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28396657/the-activity-of-a-hexameric-m17-metallo-aminopeptidase-is-associated-with-survival-of-mycobacterium-tuberculosis
#19
Andre F Correa, Izabela M D Bastos, David Neves, Andre Kipnis, Ana P Junqueira-Kipnis, Jaime M de Santana
Mycobacterium tuberculosis is one of the most prevalent human pathogens causing millions of deaths in the last years. Moreover, tuberculosis (TB) treatment has become increasingly challenging owing to the emergence of multidrug resistant M. tuberculosis strains. Thus, there is an immediate need for the development of new anti-TB drugs. Proteases appear to be a promising approach and may lead to shortened and effective treatments for drug-resistant TB. Although the M. tuberculosis genome predicts more than 100 genes encoding proteases, only a few of them have been studied...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28394582/multiplex-paper-based-colorimetric-dna-sensor-using-pyrrolidinyl-peptide-nucleic-acid-induced-agnps-aggregation-for-detecting-mers-cov-mtb-and-hpv-oligonucleotides
#20
Prinjaporn Teengam, Weena Siangproh, Adisorn Tuantranont, Tirayut Vilaivan, Orawon Chailapakul, Charles S Henry
The development of simple fluorescent and colorimetric assays that enable point-of-care DNA and RNA detection has been a topic of significant research because of the utility of such assays in resource limited settings. The most common motifs utilize hybridization to a complementary detection strand coupled with a sensitive reporter molecule. Here, a paper-based colorimetric assay for DNA detection based on pyrrolidinyl peptide nucleic acid (acpcPNA)-induced nanoparticle aggregation is reported as an alternative to traditional colorimetric approaches...
April 27, 2017: Analytical Chemistry
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