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peptides and tuberculosis

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https://www.readbyqxmd.com/read/28318770/expression-of-cathepsin-s-in-bcg-converts-it-into-a-pro-apoptotic-and-highly-immunogenic-strain
#1
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
#2
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
#3
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
#4
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
https://www.readbyqxmd.com/read/28222677/molecular-characterization-of-invasive-capsule-null-neisseria-meningitidis-in-south-africa
#5
Karistha Ganesh, Mushal Allam, Nicole Wolter, Holly B Bratcher, Odile B Harrison, Jay Lucidarme, Ray Borrow, Linda de Gouveia, Susan Meiring, Monica Birkhead, Martin C J Maiden, Anne von Gottberg, Mignon du Plessis
BACKGROUND: The meningococcal capsule is an important virulence determinant. Unencapsulated meningococci lacking capsule biosynthesis genes and containing the capsule null locus (cnl) are predominantly non-pathogenic. Rare cases of invasive meningococcal disease caused by cnl isolates belonging to sequence types (ST) and clonal complexes (cc) ST-845 (cc845), ST-198 (cc198), ST-192 (cc192) and ST-53 (cc53) have been documented. The clinical significance of these isolates however remains unclear...
February 21, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28218580/circulating-cathelicidin-ll-37-in-adult-patients-with-pulmonary-infectious-diseases
#6
Karol Majewski, Paulina Żelechowska, Ewa Brzezińska-Błaszczyk
PURPOSE: The antimicrobial peptide cathelicidin LL-37 plays a role in the immune response in the course of lung infections; however, the exact role of LL-37 in defense mechanisms against bacteria within the respiratory tract is has not been precisely described. The aim of our study was to evaluate LL-37 concentrations in the serum of pulmonary tuberculosis (TB) patients, patients with pneumonia caused by Gram-positive and Gram-negative bacteria and to compare them with those of healthy subjects...
February 19, 2017: Clinical and Investigative Medicine. Médecine Clinique et Experimentale
https://www.readbyqxmd.com/read/28205097/identifying-and-characterising-ppe7-rv0354c-high-activity-binding-peptides-and-their-role-in-inhibiting-cell-invasion
#7
Diana P Díaz, Marisol Ocampo, Yahson Varela, Hernando Curtidor, Manuel A Patarroyo, Manuel E Patarroyo
This study was aimed at characterising the PPE7 protein from the PE/PPE protein family. The presence and transcription of the rv0354c gene in the Mycobacterium tuberculosis complex was determined and the subcellular localisation of the PPE7 protein on mycobacterial membrane was confirmed by immunoelectron microscope. Two peptides were identified as having high binding activity (HABPs) and were tested in vitro regarding the invasion of Mycobacterium tuberculosis H37Rv. HABP 39224 inhibited invasion in A549 epithelial cells and U937 macrophages by more than 50%, whilst HABP 39225 inhibited invasion by 40% in U937 cells...
February 15, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28192214/immune-recognition-surface-construction-of-mycobacterium-tuberculosis-epitope-specific-antibody-responses-in-tuberculosis-patients-identified-by-peptide-microarrays
#8
REVIEW
Davide Valentini, Martin Rao, Giovanni Ferrara, Marc Perkins, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Understanding of humoral immune responses in tuberculosis (TB) is gaining interest, since B-cells and antibodies may be important in diagnosis as well as protective immune responses. High-content peptide microarrays (HCPM) are highly precise and reliable for gauging specific antibody responses to pathogens, as well as autoantigens. METHODS: An HCPM comprising epitopes spanning 154 proteins of Mycobacterium tuberculosis was used to gauge specific IgG antibody responses in sera of TB patients from Africa and South America...
February 10, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28161459/peptide-microarray-based-characterization-of-antibody-responses-to-host-proteins-after-bacille-calmette-gu%C3%A3-rin-vaccination
#9
REVIEW
Davide Valentini, Martin Rao, Lalit Rane, Sayma Rahman, Rebecca Axelsson-Robertson, Rainer Heuchel, Matthias Löhr, Daniel Hoft, Susanna Brighenti, Alimuddin Zumla, Markus Maeurer
BACKGROUND: Bacille Calmette-Guérin (BCG) is the world's most widely distributed vaccine, used against tuberculosis (TB), in cancer immunotherapy, and in autoimmune diseases due to its immunomodulatory properties. To date, the effect of BCG vaccination on antibody responses to host proteins has not been reported. High-content peptide microarrays (HCPM) offer a unique opportunity to gauge specific humoral immune responses. METHODS: The sera of BCG-vaccinated healthy adults were tested on a human HCPM platform (4953 randomly selected epitopes of human proteins) to detect specific immunoglobulin gamma (IgG) responses...
February 2, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28159576/humoral-immune-profiling-of-mycobacterial-antigen-recognition-in-sarcoidosis-and-l%C3%A3-fgren-s-syndrome-using-high-content-peptide-microarrays
#10
REVIEW
Giovanni Ferrara, Davide Valentini, Martin Rao, Jan Wahlström, Johan Grunewald, Lars-Olof Larsson, Susanna Brighenti, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
INTRODUCTION: Sarcoidosis is considered an idiopathic granulomatous disease, although similar immunological and clinical features with tuberculosis (TB) suggest mycobacterial involvement in its pathogenesis. High-content peptide microarrays (HCPM) may help to decipher mycobacteria-specific antibody reactivity in sarcoidosis. METHODS: Serum samples from patients with sarcoidosis, Löfgren's syndrome, and TB, as well as from healthy individuals (12/group), were tested on HCPM containing 5964 individual peptides spanning 154 Mycobacterium tuberculosis proteins displayed as 15-amino acid stretches...
January 31, 2017: International Journal of Infectious Diseases: IJID
https://www.readbyqxmd.com/read/28120876/mycofactocin-associated-mycobacterial-dehydrogenases-with-non-exchangeable-nad-cofactors
#11
Daniel H Haft, Phillip G Pierce, Stephen J Mayclin, Amy Sullivan, Anna S Gardberg, Jan Abendroth, Darren W Begley, Isabelle Q Phan, Bart L Staker, Peter J Myler, Vasilios M Marathias, Donald D Lorimer, Thomas E Edwards
During human infection, Mycobacterium tuberculosis (Mtb) survives the normally bacteriocidal phagosome of macrophages. Mtb and related species may be able to combat this harsh acidic environment which contains reactive oxygen species due to the mycobacterial genomes encoding a large number of dehydrogenases. Typically, dehydrogenase cofactor binding sites are open to solvent, which allows NAD/NADH exchange to support multiple turnover. Interestingly, mycobacterial short chain dehydrogenases/reductases (SDRs) within family TIGR03971 contain an insertion at the NAD binding site...
January 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28115505/identification-of-mycobacterial-rplj-l10-and-rpsa-s1-proteins-as-novel-targets-for-cd4-t-cells
#12
Alison J Johnson, Steven C Kennedy, Cecilia S Lindestam Arlehamn, Michael F Goldberg, Neeraj K Saini, Jiayong Xu, Sinu Paul, Subray S Hegde, John S Blanchard, John Chan, William R Jacobs, Alessandro Sette, Steven A Porcelli
Tuberculosis (TB) due to Mycobacterium tuberculosis (Mtb) remains a major global infectious disease problem, and a more efficacious vaccine is urgently needed for control and prevention of disease caused by this organism. We previously reported a genetically modified strain of Mycobacterium smegmatis called IKEPLUS as a promising TB vaccine candidate. Since protective immunity induced by IKEPLUS is dependent on antigen-specific CD4(+) T cell memory, we hypothesized that the specificity of the CD4(+) T cell response was a critical feature of this protection...
January 23, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28111615/the-effects-of-first-line-anti-tuberculosis-drugs-on-the-actions-of-vitamin-d-in-human-macrophages
#13
Supavit Chesdachai, Susu M Zughaier, Li Hao, Russell R Kempker, Henry M Blumberg, Thomas R Ziegler, Vin Tangpricha
Tuberculosis (TB) is a major global health problem. Patients with TB have a high rate of vitamin D deficiency, both at diagnosis and during the course of treatment with anti-tuberculosis drugs. Although data on the efficacy of vitamin D supplementation on Mycobacterium tuberculosis (Mtb) clearance is uncertain from randomized controlled trials (RCTs), vitamin D enhances the expression of the anti-microbial peptide human cathelicidin (hCAP18) in cultured macrophages in vitro. One possible explanation for the mixed (primarily negative) results of RCTs examining vitamin D treatment in TB infection is that anti-TB drugs given to enrolled subjects may impact actions of vitamin D to enhance cathelicidin in macrophages...
December 2016: Journal of Clinical & Translational Endocrinology
https://www.readbyqxmd.com/read/28108375/the-role-of-pattern-recognition-receptors-in-lung-sarcoidosis
#14
Esmaeil Mortaz, Ian M Adcock, Atefhe Abedini, Arda Kiani, Mehdi Kazempour-Dizaji, Masoud Movassaghi, Johan Garssen
Sarcoidosis is a granulomatous disorder of unknown etiology. Infection, genetic factors, autoimmunity and an aberrant innate immune system have been explored as potential causes of sarcoidosis. The etiology of sarcoidosis remains unknown, and it is thought that it might be caused by an infectious agent in a genetically predisposed, susceptible host. Inflammation results from recognition of evolutionarily conserved structures of pathogens (Pathogen-associated molecular patterns, PAMPs) and/or from reaction to tissue damage associated patterns (DAMPs) through recognition by a limited number of germ line-encoded pattern recognition receptors (PRRs)...
January 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28106929/conformational-analysis-of-an-antibacterial-cyclodepsipeptide-active-against-m-tuberculosis-by-a-combined-roe-and-rdc-analysis
#15
Maic Fredersdorf, Michael Kurz, Armin Bauer, Marc-Olivier Ebert, Carla Rigling, Laurie Lannes, Christina Thiele
Griselimycin (GM) and methylgriselimycin (MGM), naturally produced by microorganisms of the genus Streptomyces, are cyclic depsipeptides composed of ten amino acids. They exhibit antibacterial activity against mycobacterium species by inhibiting the sliding clamp of prokaryotic DNA polymerase III and are therefore considered as potential anti-tuberculosis drugs. The difference between both peptides is the presence of L -(R)-4-methylproline in MGM instead of L -proline in GM at position 8 of the amino acid sequence...
January 20, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28097645/bacterial-subversion-of-camp-signalling-inhibits-cathelicidin-expression-which-is-required-for-innate-resistance-to-mycobacterium-tuberculosis
#16
Shashank Gupta, Kathryn Winglee, Richard Gallo, William R Bishai
Antimicrobial peptides such as cathelicidins are an important component of innate immune defence against inhaled microorganisms and have demonstrated antimicrobial activity against Mycobacterium tuberculosis with in vitro models. Despite this, little is known about the regulation and expression of cathelicidin during tuberculosis in vivo. We sought to determine whether the cathelicidin-related antimicrobial peptide (Cramp) gene, the murine functional homologue of the human cathelicidin gene (CAMP or LL-37), is required for regulating protective immunity during M...
January 18, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28096545/thiazomycin-nocathiacin-and-analogs-show-strong-activity-against-clinical-strains-of-drug-resistant-mycobacterium-tuberculosis
#17
Sheo B Singh, Libo Xu, Peter T Meinke, Natalia Kurepina, Barry N Kreiswirth, David B Olsen, Katherine Young
Thiazolyl peptides are a class of natural products with potent Gram-positive antibacterial activities. Lack of aqueous solubility precluded this class of compounds from advancing to clinical evaluations. Nocathiacins and thiazomycins are sub-classes of thiazolyl peptides that are endowed with structural features amenable for chemical modifications. Semi-synthetic modifications of nocathiacin led to a series of analogs with improved water solubility, while retaining potency and antibacterial spectrum. We studied the activities of a selection of two natural products (nocathiacin and thiazomycin) as well as seven polar semi-synthetic analogs against twenty clinical strains of Mycobacterium tuberculosis with MDR phenotypes...
January 18, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28078341/the-role-of-uv-radiation-and-vitamin-d-in-the-seasonality-and-outcomes-of-infectious-disease
#18
Abhimanyu, Anna K Coussens
The seasonality of infectious disease outbreaks suggests that environmental conditions have a significant effect on disease risk. One of the major environmental factors that can affect this is solar radiation, primarily acting through ultraviolet radiation (UVR), and its subsequent control of vitamin D production. Here we show how UVR and vitamin D, which are modified by latitude and season, can affect host and pathogen fitness and relate them to the outcomes of bacterial, viral and vector-borne infections...
January 12, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/28075068/binding-and-processing-of-%C3%AE-lactam-antibiotics-by-the-transpeptidase-ldtmt2-from-mycobacterium-tuberculosis
#19
Eva Maria Steiner, Gunter Schneider, Robert Schnell
β-lactam antibiotics represent a novel direction in the chemotherapy of tuberculosis that brings the peptidoglycan layer of the complex mycobacterial cell wall in focus as a therapeutic target. Peptidoglycan stability in Mycobacterium tuberculosis, especially during infection, relies on the nonconventional peptide cross-links formed by l,d-transpeptidases. These enzymes are known to be inhibited by β-lactams, primarily carbapenems, leading to a stable covalent modification at the enzyme active site. A panel of 16 β-lactam antibiotics was characterized by inhibition kinetics, mass spectrometry, and x-ray crystallography to identify efficient compounds and study their action on the essential transpeptidase, LdtMt2 ...
January 11, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28060545/safety-and-immunogenicity-of-adenovirus-35-tb-vaccine-candidate-in-adults-with-active-or-previous-tb-a-randomized-trial
#20
Richard N van Zyl-Smit, Aliasgar Esmail, Mary E Bateman, Rodney Dawson, Jonathan Goldin, Eva van Rikxoort, Macaya Douoguih, Maria Grazia Pau, Jerald C Sadoff, J Bruce McClain, Margaret Ann Snowden, Jacqueline Benko, David A Hokey, Kathryn Tucker Rutkowski, Andrew Graves, Barbara Shepherd, Sadritdin Ishmukhamedov, Benjamin M N Kagina, Brian Abel, Willem A Hanekom, Thomas J Scriba, Eric D Bateman
RATIONALE: Administration of tuberculosis vaccines in participants with previous or current pulmonary tuberculosis may have the potential for causing harmful post-vaccination immunological (Koch-type) reactions. OBJECTIVES: To assess the safety and immunogenicity of three dose levels of the AERAS-402 live, replication-deficient adenovirus 35-vectored tuberculosis candidate vaccine, containing three mycobacterial antigens, in individuals with current or previous pulmonary tuberculosis...
January 6, 2017: American Journal of Respiratory and Critical Care Medicine
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