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peptides and tuberculosis

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https://www.readbyqxmd.com/read/28496439/bortezomib-warhead-switch-confers-dual-activity-against-mycobacterial-caseinolytic-protease-and-proteasome-and-selectivity-against-human-proteasome
#1
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
#2
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
#3
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
#4
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 5, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28446822/anti-mycobacterium-activity-of-microbial-peptides-in-a-silkworm-infection-model-with-mycobacterium-smegmatis
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28386154/the-exploration-of-peptide-biomarkers-in-malignant-pleural-effusion-of-lung-cancer-using-matrix-assisted-laser-desorption-ionization-time-of-flight-mass-spectrometry
#11
Jing Xu, Bin Xu, Chuanhao Tang, Xiaoyan Li, Haifeng Qin, Weixia Wang, Hong Wang, Zhongyuan Wang, Liangliang Li, Zhihua Li, Hongjun Gao, Kun He, Xiaoqing Liu
Background. Diagnoses of malignant pleural effusion (MPE) are a crucial problem in clinics. In our study, we compared the peptide profiles of MPE and tuberculosis pleural effusion (TPE) to investigate the value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) in diagnosis of MPE. Material and Methods. The 46 MPE and 32 TPE were randomly assigned to training set and validation set. Peptides were isolated by weak cation exchange magnetic beads and peaks in the m/z range of 800-10000 Da were analyzed...
2017: Disease Markers
https://www.readbyqxmd.com/read/28384546/in%C3%A2-vitro-biological-evaluation-of-new-antimycobacterial-salicylanilide-tuftsin-conjugates
#12
Zsuzsa Baranyai, Martin Krátký, Rudolf Vosátka, Eleonóra Szabó, Zsuzsanna Senoner, Sándor Dávid, Jiřina Stolaříková, Jarmila Vinšová, Szilvia Bősze
Tuberculosis is caused by Mycobacterium tuberculosis, an intracellular pathogen that can survive in host cells, mainly in macrophages. An increase of multidrug-resistant tuberculosis qualifies this infectious disease as a major public health problem worldwide. The cellular uptake of the antimycobacterial agents by infected host cells is limited. Our approach is to enhance the cellular uptake of the antituberculars by target cell-directed delivery using drug-peptide conjugates to achieve an increased intracellular efficacy...
March 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28372590/proteomic-analysis-of-protein-purified-derivative-of-mycobacterium-bovis
#13
Sante Roperto, Mariaconcetta Varano, Valeria Russo, Roberta Lucà, Monica Cagiola, Marco Gaspari, Dora Maria Ceccarelli, Giovanni Cuda, Franco Roperto
BACKGROUND: Tuberculin skin test based on in vivo intradermal inoculation of purified protein derivative from Mycobacterium bovis (bPPD) is the diagnostic test for the control and surveillance of bovine tuberculosis (bTB). METHODS: Proteomic analysis was performed on different bPPD preparations from M. bovis, strain AN5. Proteins were precipitated from bPPD solutions by TCA precipitation. The proteome of bPPD preparations was investigated by bottom-up proteomics, which consisted in protein digestion and nano-LC-MS/MS analysis...
April 3, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28355052/design-synthesis-and-experimental-validation-of-peptide-ligands-targeting-mycobacterium-tuberculosis-%C3%AF-factors
#14
Sneha Vishwanath, Sunaina Banerjee, Anil K Jamithireddy, Narayanaswamy Srinivasan, Balasubramanian Gopal, Jayanta Chatterjee
Transcription in prokaryotes is a multistep process and is primarily regulated at the initiation stage. σ factors are involved in promoter recognition and thus govern prokaryotic gene expression. Mycobacterium tuberculosis (Mtb) σ factors have been previously suggested as important drug targets through large-scale genome analyses. Here we demonstrate the feasibility of specific targeting of Mtb σ factors using designed peptides. A peptide library was generated using three-dimensional structural features corresponding to the interface regions of σ factors and the RNA polymerase...
April 12, 2017: Biochemistry
https://www.readbyqxmd.com/read/28348866/integrated-computational-prediction-and-experimental-validation-identifies-promiscuous-t-cell-epitopes-in-the-proteome-of-mycobacterium-bovis
#15
Damien Farrell, Gareth Jones, Christopher Pirson, Kerri Malone, Kevin Rue-Albrecht, Anthony J Chubb, Martin Vordermeier, Stephen V Gordon
The discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use in control programmes against human tuberculosis (TB) and bovine tuberculosis (bTB). Identification of potential epitopes recognised by CD4(+) T cells requires prediction of peptide binding to MHC class-II, an obligatory prerequisite for T cell recognition. To comprehensively prioritise potential MHC-II-binding epitopes from Mycobacterium bovis, the agent of bTB and zoonotic TB in humans, we integrated three binding prediction methods with the M...
August 2016: Microbial Genomics
https://www.readbyqxmd.com/read/28348223/quantification-of-circulating-mycobacterium-tuberculosis-antigen-peptides-allows-rapid-diagnosis-of-active-disease-and-treatment-monitoring
#16
Chang Liu, Zhen Zhao, Jia Fan, Christopher J Lyon, Hung-Jen Wu, Dobrin Nedelkov, Adrian M Zelazny, Kenneth N Olivier, Lisa H Cazares, Steven M Holland, Edward A Graviss, Ye Hu
Tuberculosis (TB) is a major global health threat, resulting in an urgent unmet need for a rapid, non-sputum-based quantitative test to detect active Mycobacterium tuberculosis (Mtb) infections in clinically diverse populations and quickly assess Mtb treatment responses for emerging drug-resistant strains. We have identified Mtb-specific peptide fragments and developed a method to rapidly quantify their serum concentrations, using antibody-labeled and energy-focusing porous discoidal silicon nanoparticles (nanodisks) and high-throughput mass spectrometry (MS) to enhance sensitivity and specificity...
April 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28318770/expression-of-cathepsin-s-in-bcg-converts-it-into-a-pro-apoptotic-and-highly-immunogenic-strain
#17
Alice Lau, Vijender Singh, Hafid Soualhine, Zakaria Hmama
BACKGROUND: BCG vaccine, introduced almost 100years ago, is the only option to prevent TB disease. It effectively protects newborns from meningeal TB but fails to prevent adult pulmonary TB. TB kills 1.3million people annually in areas where BCG vaccination is widely practiced. Thus, more effective TB vaccines are urgently needed. Others and we have shown that BCG mimics features of virulent M. tuberculosis, in particular attenuation of essential macrophage functions such as phagosome maturation and antigen presentation...
March 16, 2017: Vaccine
https://www.readbyqxmd.com/read/28314993/comparative-analysis-of-internalisation-haemolytic-cytotoxic-and-antibacterial-effect-of-membrane-active-cationic-peptides-aspects-of-experimental-setup
#18
Kata Horváti, Bernadett Bacsa, Tamás Mlinkó, Nóra Szabó, Ferenc Hudecz, Ferenc Zsila, Szilvia Bősze
Cationic peptides proved fundamental importance as pharmaceutical agents and/or drug carrier moieties functioning in cellular processes. The comparison of the in vitro activity of these peptides is an experimental challenge and a combination of different methods, such as cytotoxicity, internalisation rate, haemolytic and antibacterial effect, is necessary. At the same time, several issues need to be addressed as the assay conditions have a great influence on the measured biological effects and the experimental setup needs to be optimised...
March 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28244701/is-low-serum-25-hydroxyvitamin-d-a-possible-link-between-pulmonary-tuberculosis-and-type-2-diabetes
#19
Qiuzhen Wang, Aiguo Ma, Xiuxia Han, Huizhen Zhang, Shanliang Zhao, Hui Liang, Jing Cai, Frans J Kok, Evert G Schouten
BACKGROUND AND OBJECTIVES: Although vitamin D is implicated in the generation of anti-microbial peptide cathelicidin, which plays a key role against pulmonary tuberculosis (PTB), and may have an inverse association with the risk of type 2 diabetes (DM), its role in the co-existence of these two diseases (PTB-DM) is still uncertain. This study explored the association of vitamin D status with prevalent PTB, PTB-DM and DM. METHODS AND STUDY DESIGN: We randomly selected 130 PTB patients, 90 PTB-DM, 91 DM and 134 controls...
March 2017: Asia Pacific Journal of Clinical Nutrition
https://www.readbyqxmd.com/read/28237038/local-targeting-nf-%C3%AE%C2%BAb-in-the-lung-tissue-of-tb-infected-mice-diminishes-the-level-of-pathology
#20
Galena Shepelkova, Vladimir Evstifeev, Tatiana Kondratieva, Irina Bocharova, Mikhail Averbakh, Alexander Apt
Mice of the genetically TB-susceptible strain I/St were infected with ∼100 CFU of Mycobacterium tuberculosis strain H37Rv, and after week 3 post-infection treated by inhalations of the NBD peptide selectively blocking NF-κB activation pathway. This therapy resulted in a pronounced attenuation of lung pathology and down-regulation of the expression of several genes encoding major inflammatory molecules, but did not diminish the level of mycobacterial multiplication in the lungs.
March 2017: Tuberculosis
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