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peptides and tuberculosis

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https://www.readbyqxmd.com/read/29777693/cleavage-of-molybdopterin-synthase-moad-moae-linear-fusion-by-jamm-mpn-domain-containing-metalloprotease-dr0402-from-deinococcus-radiodurans
#1
Yoon-Mo Yang, Young-Bin Won, Chang-Jun Ji, Jung-Hoon Kim, Su-Hyun Ryu, Youn-Ha Ok, Jin-Won Lee
Molybdenum cofactor (Moco), molybdopterin (MPT) complexed with molybdenum, is an essential cofactor required for the catalytic center of diverse enzymes in all domains of life. Since Moco cannot be taken up as a nutrient unlike many other cofactors, Moco requires de novo biosynthesis. During the synthesis of MPT, the sulfur atom on the C-terminus of MoaD is transferred to cyclic pyranopterin monophosphate (cPMP) which is bound in the substrate pocket of MoaE. MoaD is a ubiquitin-like (Ubl) protein and has a C-terminal di-Gly motif which is a common feature of Ubl proteins...
May 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29772011/induction-of-influenza-specific-local-cd8-t-cells-in-the-respiratory-tract-after-aerosol-delivery-of-vaccine-antigen-or-virus-in-the-babraham-inbred-pig
#2
Katie Tungatt, Garry Dolton, Sophie B Morgan, Meriem Attaf, Anna Fuller, Thomas Whalley, Johanneke D Hemmink, Emily Porter, Barbara Szomolay, Maria Montoya, John A Hammond, John J Miles, David K Cole, Alain Townsend, Mick Bailey, Pierre J Rizkallah, Bryan Charleston, Elma Tchilian, Andrew K Sewell
There is increasing evidence that induction of local immune responses is a key component of effective vaccines. For respiratory pathogens, for example tuberculosis and influenza, aerosol delivery is being actively explored as a method to administer vaccine antigens. Current animal models used to study respiratory pathogens suffer from anatomical disparity with humans. The pig is a natural and important host of influenza viruses and is physiologically more comparable to humans than other animal models in terms of size, respiratory tract biology and volume...
May 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29765542/smar1-inhibits-wnt-%C3%AE-catenin-signaling-and-prevents-colorectal-cancer-progression
#3
Nandaraj Taye, Aftab Alam, Suvankar Ghorai, Deya Ghosh Chatterji, Apoorva Parulekar, Devraj Mogare, Snahlata Singh, Pallabi Sengupta, Subhrangsu Chatterjee, Manoj Kumar Bhat, Manas Kumar Santra, Prabhakar Budha Salunkhe, Susan Kling Finston, Samit Chattopadhyay
Reduced expression of Scaffold/Matrix Attachment Region Binding Protein 1 (SMAR1) is associated with various cancers resulting in poor prognosis of the diseases. However, the precise underlying mechanism elucidating the loss of SMAR1 requires ongoing study. Here, we show that SMAR1 is highly downregulated during aberrant Wnt3a signaling due to proteasomal degradation and predicted poor prognosis of colorectal cancer. However, substitution mutation (Arginine and Lysine to Alanine) in the D-box elements of SMAR1 viz...
April 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29747543/activation-of-%C3%AE-and-%C3%AE-carbonic-anhydrases-from-pathogenic-bacteria-with-tripeptides
#4
Azzurra Stefanucci, Andrea Angeli, Marilisa Pia Dimmito, Grazia Luisi, Sonia Del Prete, Clemente Capasso, William A Donald, Adriano Mollica, Claudiu T Supuran
Six tripeptides incorporating acidic amino acid residues were prepared for investigation as activators of β- and γ-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic bacteria Vibrio cholerae, Mycobacterium tuberculosis, and Burkholderia pseudomallei. The primary amino acid residues that are involved in the catalytic mechanisms of these CA classes are poorly understood, although glutamic acid residues near the active site appear to be involved. The tripeptides that contain Glu or Asp residues can effectively activate VchCAβ and VchCAγ (enzymes from V...
December 2018: Journal of Enzyme Inhibition and Medicinal Chemistry
https://www.readbyqxmd.com/read/29738954/antibacterial-and-anti-tb-tat-peptidomimetics-with-improved-efficacy-and-half-life
#5
Govind S Bhosle, Laxman Nawale, Amar M Yeware, Dhiman Sarkar, Moneesha Fernandes
Non-natural antimicrobial peptides are ideal as next-generation antibiotics because of their ability to circumvent the problems of drug resistance and in vivo instability. We report novel all-α- and α,γ-mixed Tat peptide analogues as potential antibacterial and anti-TB agents. These peptides have broad spectrum antibacterial activities against Gram-positive (MICs 0.61 ± 0.03 to 1.35 ± 0.21 μM with the peptide γTatM4) and Gram-negative (MICs 0.71 ± 0.005 to 1.26 ± 0.02 μM with γTatM4) bacteria and are also effective against active and dormant forms of Mycobacterium tuberculosis, including strains that are resistant to rifampicin and isoniazid...
April 30, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29722065/the-structure-of-the-n-terminal-module-of-the-cell-wall-hydrolase-ripa-and-its-role-in-regulating-catalytic-activity
#6
Eva Maria Steiner, Jeppe Lyngsø, Jodie E Guy, Gleb Bourenkov, Ylva Lindqvist, Thomas R Schneider, Jan Skov Pedersen, Gunter Schneider, Robert Schnell
RipA plays a vital role during cell division of Mycobacterium tuberculosis by degrading the cell wall peptidoglycan at the septum, allowing daughter cell separation. The peptidoglycan degrading activity relies on the NlpC/P60 domain, and as it is potentially harmful when deregulated, spatial and temporal control is necessary in this process. The N-terminal domain of RipA has been proposed to play an inhibitory role blocking the C-terminal NlpC/P60 domain. Accessibility of the active site cysteine residue is however not limited by the presence of the N-terminal domain, but by the lid-module of the inter-domain linker, which is situated in the peptide binding groove of the crystal structures of the catalytic domain...
May 2, 2018: Proteins
https://www.readbyqxmd.com/read/29718298/genomic-structure-and-tissue-expression-of-the-nk-lysin-gene-family-in-bison
#7
Mi Ok Lee, Lauren Dobson, Brian W Davis, Loren Skow, James Derr, James E Womack
Antimicrobial peptides (AMPs) are a class of natural peptides with varying numbers of amino acids. They are principal components of innate immunity in vertebrates, encoding natural antibiotics and providing a protective response against a broad range of microbes including those responsible for tuberculosis, an important disease in bison. NK-lysins are AMPs that have been described in various organisms and are coded by a single gene in several mammalian species, including human. Recently, we described a family of four NK-lysin genes in cattle...
April 28, 2018: Journal of Heredity
https://www.readbyqxmd.com/read/29717013/quorum-sensing-extracellular-death-peptides-enhance-the-endoribonucleolytic-activities-of-mycobacterium-tuberculosis-mazf-toxins
#8
Akanksha Nigam, Sathish Kumar, Hanna Engelberg-Kulka
mazEF is a toxin-antitoxin module located on chromosomes of most bacteria. MazF toxins are endoribonucleases antagonized by MazE antitoxins. Previously, we characterized several quorum sensing peptides called "<u>e</u>xtracellular <u>d</u>eath <u>f</u>actors" (EDFs). When secreted from bacterial cultures, EDFs induce interspecies cell death. EDFs also enhance the endoribonucleolytic activity of Escherichia coli MazF. Mycobacterium tuberculosis carries several mazEF modules...
May 1, 2018: MBio
https://www.readbyqxmd.com/read/29685013/status-of-cathelicidin-il-37-cytokine-tnf-and-vitamin-d-in-patients-with-pulmonary-tuberculosis
#9
K Majewski, J Agier, E Kozłowska, E Brzezińska-Błaszczyk
Development of Mycobacterium tuberculosis (Mtb) infection depends on the ability of the host to elicit the protective immune response to the pathogen. Cathelicidin plays a role in antibacterial innate immunity mechanisms. This peptide contributes to the barrier function of respiratory epithelium and takes part in controlling pulmonary bacterial infections. LL-37 (leucine-leucine-37) is involved in host defense and innate immune response to mycobacterial infections, as well. This study aims to evaluate the serum concentrations of LL-37 in individuals with active pulmonary tuberculosis (TB) and to determine whether any correlations between peptide LL-37, tumor necrosis factor (TNF) and vitamin D serum levels exist...
March 2018: Journal of Biological Regulators and Homeostatic Agents
https://www.readbyqxmd.com/read/29669198/surface-layer-modification-of-plga-nanoparticles-with-targeting-peptide-a-convenient-synthetic-route-for-pluronic-f127-tuftsin-conjugate
#10
Kata Horváti, Gergo Gyulai, Antal Csámpai, János Rohonczy, Eva Kiss, Szilvia Erika Bosze
Nanoparticles consist of biodegradable poly(D,L-lactic-co-glycolic acid) (PLGA) are promising carriers for drug molecules to improve the treatment of tuberculosis. Surface modifiers, such as Pluronic F127, are essential for biocompatibility and for the protection against particle aggregation. This study demonstrates a successful approach to conjugate Pluronic F127 coated PLGA nanoparticles with Tuftsin, which has been reported as a macrophage-targeting peptide. Transformation of Pluronic F127 hydroxyl groups - which have limited reactivity - into aldehyde groups provide a convenient way to bind aminooxy-peptide derivatives in one step reaction...
April 18, 2018: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/29662482/targeting-mycobacterium-tuberculosis-antigens-to-dendritic-cells-via-the-dc-specific-icam3-grabbing-nonintegrin-receptor-induces-strong-t-helper-1-immune-responses
#11
Lis Noelia Velasquez, Philipp Stüve, Maria Virginia Gentilini, Maxine Swallow, Judith Bartel, Nils Yngve Lycke, Daniel Barkan, Mariana Martina, Hugo D Lujan, Hakan Kalay, Yvette van Kooyk, Tim D Sparwasser, Luciana Berod
Tuberculosis remains a major global health problem and efforts to develop a more effective vaccine have been unsuccessful so far. Targeting antigens (Ags) to dendritic cells (DCs) in vivo has emerged as a new promising vaccine strategy. In this approach, Ags are delivered directly to DCs via antibodies that bind to endocytic cell-surface receptors. Here, we explored DC-specific-ICAM3-grabbing-nonintegrin (DC-SIGN) targeting as a potential vaccine against tuberculosis. For this, we made use of the hSIGN mouse model that expresses human DC-SIGN under the control of the murine CD11c promoter...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29650461/towards-designing-a-synthetic-antituberculosis-vaccine-the-rv3587c-peptide-inhibits-mycobacterial-entry-to-host-cells
#12
Mary Lilian Carabali-Isajar, Marisol Ocampo, Deisy Carolina Rodriguez, Magnolia Vanegas, Hernando Curtidor, Manuel Alfonso Patarroyo, Manuel Elkin Patarroyo
Mycobacterium tuberculosis is considered one of the most successful pathogens in the history of mankind, having caused 1.7 million deaths in 2016. The amount of resistant and extensively resistant strains has increased; BCG has been the only vaccine to be produced in more than 100 years though it is still unable to prevent the disease's most disseminated form in adults; pulmonary tuberculosis. The search is thus still on-going for candidate antigens for an antituberculosis vaccine. This paper reports the use of a logical and rational methodology for finding such antigens, this time as peptides derived from the Rv3587c membrane protein...
April 4, 2018: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29623875/use-of-a-leukocyte-targeted-peptide-probe-as-a-potential-tracer-for-imaging-the-tuberculosis-granuloma
#13
Landon W Locke, Shankaran Kothandaraman, Michael Tweedle, Sarah Chaney, Daniel J Wozniak, Larry S Schlesinger
Granulomas are the histopathologic hallmark of tuberculosis (TB), both in latency and active disease. Diagnostic and therapeutic strategies that specifically target granulomas have not been developed. Our objective is to develop a probe for imaging relevant immune cell populations infiltrating the granuloma. We report the binding specificity of Cyanine 3 (Cy3)-labeled cFLFLFK-PEG12 to human leukocytes and cellular constituents within a human in vitro granuloma model. We also report use of the probe in in vivo studies using a mouse model of lung granulomatous inflammation...
January 2018: Tuberculosis
https://www.readbyqxmd.com/read/29589538/antimicrobial-peptides-for-the-treatment-of-pulmonary-tuberculosis-allies-or-foes
#14
Bruno Rivas-Santiago, Flor Torres-Juarez
Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of world health organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the antimicrobial peptides (AMPs)...
March 27, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29559125/evaluation-of-a-synthetic-peptide-for-the-detection-of-anti-mycobacterium-tuberculosis-curli-pili-igg-antibodies-in-patients-with-pulmonary-tuberculosis
#15
Natasha Naidoo, Balakrishna Pillay, Martin Bubb, Alexander Pym, Thamsanqa Chiliza, Kogieleum Naidoo, Thumbi Ndung'u, Victoria O Kasprowicz, Manormoney Pillay
Tuberculosis (TB) remains a serious threat in underdeveloped areas. Mycobacterium tuberculosis curli pili (MTP), a virulence factor, is a potential biomarker for a reliable point of care (POC) test and was evaluated for its ability to react with Immunoglobulin G (IgG) in TB patients. An MTP synthetic peptide in a slot blot assay was used to screen serum/plasma samples (n = 65) in 3 separate cohorts, including 40 TB positive (16 HIV co-infected), 20 TB negative/HIV negative patients and 5 healthy volunteers...
March 2018: Tuberculosis
https://www.readbyqxmd.com/read/29548008/limited-antimycobacterial-efficacy-of-epitope-peptide-administration-despite-enhanced-antigen-specific-cd4-t-cell-activation
#16
Joel D Ernst, Amber Cornelius, Ludovic Desvignes, Jacqueline Tavs, Brian A Norris
Infection with M. tuberculosis is associated with inconsistent and incomplete elimination of the bacteria, despite development of antigen-specific T cell responses. One mechanism employed by M. tuberculosis is to limit availability of antigen for activation of CD4 T cells. We examined the utility of systemic administration of epitope peptides to activate pre-existing T cells in mice infected with M. tuberculosis. We found that systemic peptide administration: 1) selectively activates T cells specific for the epitope peptide; 2) loads MHC class II on lung macrophages and dendritic cells; 3) activates CD4 T cells in the lung parenchyma; 4) has little antimycobacterial activity...
March 14, 2018: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29545791/functional-antigen-specific-stem-cell-memory-t-scm-cd4-t-cells-are-induced-by-human-mycobacterium-tuberculosis-infection
#17
Cheleka A M Mpande, One B Dintwe, Munyaradzi Musvosvi, Simbarashe Mabwe, Nicole Bilek, Mark Hatherill, Elisa Nemes, Thomas J Scriba
Background: Maintenance of long-lasting immunity is thought to depend on stem cell memory T cells (TSCM ), which have superior self-renewing capacity, longevity and proliferative potential compared with central memory (TCM ) or effector (TEFF ) T cells. Our knowledge of TSCM derives primarily from studies of virus-specific CD8+ TSCM . We aimed to determine if infection with Mycobacterium tuberculosis ( M. tb ), the etiological agent of tuberculosis, generates antigen-specific CD4+ TSCM and to characterize their functional ontology...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29540577/a-high-throughput-whole-blood-assay-for-analysis-of-multiple-antigen-specific-t-cell-responses-in-human-mycobacterium-tuberculosis-infection
#18
Wendy E Whatney, Neel R Gandhi, Cecilia S Lindestam Arlehamn, Azhar Nizam, Hao Wu, Melanie J Quezada, Angela Campbell, Salim Allana, Mbuyi Madeleine Kabongo, Jeremiah Khayumbi, Benson Muchiri, Joshua Ongalo, Joan Tonui, Loren E Sasser, Tawania J Fergus, Gregory Sadat Ouma, Samuel Gurrion Ouma, Allison A Beck, Mark J Mulligan, Alawode Oladele, Deepak Kaushal, Kevin P Cain, Lance Waller, Henry M Blumberg, John D Altman, Joel D Ernst, Jyothi Rengarajan, Cheryl L Day
Antigen-specific CD4 and CD8 T cells are important components of the immune response to Mycobacterium tuberculosis , yet little information is currently known regarding how the breadth, specificity, phenotype, and function of M. tuberculosis -specific T cells correlate with M. tuberculosis infection outcome in humans. To facilitate evaluation of human M. tuberculosis -specific T cell responses targeting multiple different Ags, we sought to develop a high throughput and reproducible T cell response spectrum assay requiring low blood sample volumes...
April 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29530985/the-transpeptidase-pbpa-and-noncanonical-transglycosylase-roda-of-mycobacterium-tuberculosis-play-important-roles-in-regulating-bacterial-cell-lengths
#19
Divya Arora, Yogesh Chawla, Basanti Malakar, Archana Singh, Vinay Kumar Nandicoori
The cell wall of Mycobacterium tuberculosis ( Mtb ) is a complex structure that protects the pathogen in hostile environments. Peptidoglycan (PG), which helps determine the morphology of the cell envelope, undergoes substantial remodeling under stress. This meshwork of linear chains of sugars, cross-linked through attached peptides, is generated through the sequential action of enzymes termed transglycosylases and transpeptidases. The Mtb genome encodes two classical transglycosylases and four transpeptidases, the functions of which are not fully elucidated...
April 27, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29526817/evaluation-of-spectral-libraries-and-sample-preparation-for-dia-lc-ms-analysis-of-host-cell-proteins-a-case-study-of-a-bacterially-expressed-recombinant-biopharmaceutical-protein
#20
Søren Heissel, Jakob Bunkenborg, Max Per Kristiansen, Anne Fich Holmbjerg, Marie Grimstrup, Ejvind Mørtz, Thomas Kofoed, Peter Højrup
Recombinantly expressed biopharmaceutical proteins often undergo a series of purification steps with the aim of removing contaminating material. Depending on the application of the protein, there are various requirements for the degree of purity, but host cell proteins (HCPs) will in general remain in small amounts. LC-MS has emerged as an orthogonal technique, capable of providing detailed information regarding the individual proteins. The aim of this case study was to characterize the HCPs associated with a biopharmaceutical protein, provided by Statens Serum Institut (DK), which is used in the field of tuberculosis and has not previously been studied by LC-MS...
July 2018: Protein Expression and Purification
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