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peptides and tuberculosis

Susmita K Singh, Anna-Maria Andersson, Rada Ellegård, Cecilia S Lindestam Arlehamn, Alessandro Sette, Marie Larsson, Olle Stendahl, Robert Blomgran
HIV coinfection is the most prominent risk factor for progression of Mycobacterium tuberculosis (Mtb) infection into active tuberculosis (TB) disease. The mechanisms behind the increased transition from latent to active TB in coinfected individuals have not been well elucidated at the cellular level. We hypothesized that HIV infection contributes to Mtb pathogenesis by interfering with the dendritic cell (DC)-mediated immune control. Mtb-antigen processing and presentation are key events in the immune response against TB...
October 13, 2016: American Journal of Pathology
Vikram Londhey, Meghav M Shah
INTRODUCTION: Anti-cyclic citrullinated peptide (anti-CCP) antibodies have been considered very specific for rheumatoid arthritis (RA). Some studies have shown that these antibodies can be positive in infectious diseases like TB, HIV, etc. METHODS: Fifty patients of tuberculosis both pulmonary and extra-pulmonary were enrolled in the study from inpatient and outpatient departments from May 2012 to November 2013. Anti-CCP antibody test was done in all the patient by ELISA...
May 2016: Journal of the Association of Physicians of India
Haodi Dong, Yue Lv, Deming Zhao, Paul Barrow, Xiangmei Zhou
Human tuberculosis remains a huge global public health problem with an estimated 1/3rd of the population being infected. Defensins are antibacterial cationic peptides produced by a number of cell types, most notably neutrophil granulocytes and epithelial cells. All three defensin types (α-, β-, and θ-defensins) have antibacterial activities, mainly through bacterial membrane permeabilization. Defensins are effective against Gram-negative and Gram-positive bacteria including mycobacteria and are active both intra- and extracellularly...
2016: Journal of Immunology Research
Xu Qian, Duc T M Nguyen, Yaojun Li, Jianxin Lyu, Edward A Graviss, Tony Y Hu
BACKGROUND: There is an urgent need for methods that can rapidly and accurately assess therapeutic responses in patients with active tuberculosis (TB) in order to predict treatment outcomes. Exposure to bacterial pathogens can rapidly activate the plasma contact system, triggering the release of bradykinin (BK) and its metabolite desArg(9)-bradykinin (DABK) to induce inflammation and innate immune responses. We hypothesized that serum BK and DABK levels might act as sensitive immune response signatures for changes in Mycobacterium tuberculosis (Mtb) burden, and therefore examined how serum levels of these markers corresponded with anti-TB therapy in a small cohort of active TB cases...
September 28, 2016: Tuberculosis
Elisa Petruccioli, Teresa Chiacchio, Ilaria Pepponi, Valentina Vanini, Rocco Urso, Gilda Cuzzi, Lucia Barcellini, Daniela Maria Cirillo, Fabrizio Palmieri, Giuseppe Ippolito, Delia Goletti
INTRODUCTION: QuantiFERON(®)-TB Gold Plus (QFT-Plus) is the new generation of QuantiFERON-TB Gold In-Tube test to identify latent tuberculosis infection (LTBI). QFT-Plus includes TB1 and TB2 tubes which contain selected Mycobacterium tuberculosis (Mtb) peptides designed to stimulate both CD4 and CD8 T-cells. Aim of this study is the flow cytometric characterization of the specific CD4 and CD8 T-cell responses to Mtb antigens contained within QFT-Plus. METHODS: We enrolled 27 active tuberculosis (TB) patients and 30 LTBI individuals...
October 4, 2016: Journal of Infection
Ji-Young Joo, Gil Sun Cha, Jin Chung, Ju-Youn Lee, Sung-Jo Kim, Jeomil Choi
BACKGROUND: Although periodontal pathogens show a strong association with the development of atherosclerosis, little is known about how a microorganism contributes to disease onset and progression. Oxidation of low-density lipoprotein (LDL) is a major risk factor of atherogenesis. The principal objective of our study was to evaluate the ability of peptide 19 (Pep19) of Porphyromonas gingivalis (P. gingivalis) heat shock protein (HSP) as a potent inducer of LDL oxidation, and as a secondary objective, to compare this ability with that of Pep19 from different bacteria...
October 7, 2016: Journal of Periodontology
Nancy Gupta, Satish Vedi, Dennis Y Kunimoto, Babita Agrawal, Rakesh Kumar
Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb. Peptide based subunit vaccines are attractive due to their safety and high specificity in eliciting immune responses, but small synthetic peptides are usually not very immunogenic...
September 29, 2016: Vaccine
Shilah A Bonnett, Juliane Ollinger, Susantha Chandrasekera, Stephanie Florio, Theresa O'Malley, Megan Files, Jo-Ann Jee, James Ahn, Allen Casey, Yulia Ovechkina, David Roberts, Aaron Korkegian, Tanya Parish
The general secretion (Sec) pathway is a conserved essential pathway in bacteria and is the primary route of protein export across the cytoplasmic membrane. During protein export, the signal peptidase LepB catalyzes the cleavage of the signal peptide and subsequent release of mature proteins into the extracellular space. We developed a target-based whole cell assay to screen for potential inhibitors of LepB, the sole signal peptidase in Mycobacterium tuberculosis, using a strain engineered to underexpress LepB (LepB-UE)...
September 19, 2016: ACS Infectious Diseases
Didi Bang, Siri Rytcher Andersen, Edita Vasiliauskienė, Erik Michael Rasmussen
The emergence of extensively drug-resistant tuberculosis (XDR-TB) hampers infection control. To assess the performance of an extended rapid novel molecular analysis for the detection of resistance conferring mutations to fluoroquinolones (gyrA, gyrB genes) and aminoglycosides/cyclic peptides (16S rRNA rrs gene, eis promotor region) compared to phenotypic susceptibility and sequencing, 43 multidrug-resistant (MDR) and 10 susceptible clinical isolates were analyzed. Results were compared to a previous version...
August 31, 2016: Diagnostic Microbiology and Infectious Disease
Cristal Reyna, Felix Mba Medie, Matthew M Champion, Patricia A Champion
Mass spectrometry (MS) for the detection of proteins is an indispensable tool for evaluating the biological processes of the proteome. Proteomics frequently requires proteolysis of proteins into peptide fragments. Proteins can be refractory to ideal proteolysis at the sequence level rendering them difficult to analyze by routine proteomics methods. EsxA (ESAT-6, Early Secreted Antigen, 6kDa) is a major virulence determinant of Mycobacterium tuberculosis, the cause of human tuberculosis. EsxA is routinely used to evaluate mycobacterial virulence in the laboratory and as a biomarker for tuberculosis in humans...
2016: Scientific Reports
Mark P Pereira, Julie Shi, Shana O Kelley
Mycobacterial infections are difficult to treat due to the bacterium's slow growth, ability to reside in intracellular compartments within macrophages, and resistance mechanisms that limit the effectiveness of conventional antibiotics. Developing antibiotics that overcome these challenges is therefore critical to providing a pipeline of effective antimicrobial agents. Here, we describe the synthesis and testing of a unique peptide-drug conjugate that exhibits high levels of antimicrobial activity against M...
December 11, 2015: ACS Infectious Diseases
Li Wang, Xiangying Deng, Haican Liu, Lanhua Zhao, Xiaolong You, Pei Dai, Kanglin Wan, Yanhua Zeng
Mycobacterium tuberculosis is an obligate pathogenic bacterial species in the family of Mycobacteriaceae and attracts excessive immune responses which cause pathology of the lungs in active tuberculosis. The lack of more sensitive and effective diagnosis reagents advocates a further recognition for the fast diagnostic and immunological measures for tuberculosis. Here, two 12-mer peptides with core sequences of SVSVGMKPSPRP (CS1) and TMGFTAPRFPHY (CS2) were screened from a phage display random peptide library using the purified mixed tuberculosis-positive serum as a target...
November 2016: Pathogens and Disease
Octavio Ramos-Espinosa, Sujhey Hernández-Bazán, Alejandro Francisco-Cruz, Dulce Mata-Espinosa, Jorge Barrios-Payán, Brenda Marquina-Castillo, Fernando López-Casillas, Marta Carretero, Marcela Del Río, Rogelio Hernández-Pando
Mycobacterium tuberculosis (Mtb) latent infection can lead to reactivation. The design of new strategies to prevent it is an important subject. B6D2F1 mice were infected intratracheally with a low dose of Mtb H37Rv to induce chronic infection. After 7 months, mice were treated with one dose of recombinant adenoviruses encoding TNFα, β defensin-3 and LL37. Immunosupression was induced 1 month later with corticosterone. In comparison with the control group, mice treated with adenoviruses showed significantly less bacterial load and pneumonia, the adenoviruses encoding TNFα and LL37 being the most efficient...
October 2016: Pathogens and Disease
Khomsan Supong, Paranee Sripreechasak, Somboon Tanasupawat, Kannawat Danwisetkanjana, Pranee Rachtawee, Pattama Pittayakhajonwut
The terrestrial actinomycete strain BCC71188 was identified as Streptomyces by its morphology (having spiral chain spore on the aerial mycelium), chemotaxonomy (containing LL-diaminopimelic acid in the cell wall), and 16S rRNA gene sequence analysis [showing high similarity values compared with Streptomyces samsunensis M1463(T) (99.85 %) and Streptomyces malaysiensis NBRC 16446(T) (99.40 %)]. The crude extract exhibited antimalarial against Plasmodium falciparum (IC50 0.19 μg/ml), anti-TB against Mycobacterial tuberculosis (MIC 6...
August 23, 2016: Applied Microbiology and Biotechnology
Ramiro López-Medrano, José Manuel Guerra-Laso, Eduardo López-Fidalgo, Cristina Diez-Tascón, Silvia García-García, Sara Blanco-Conde, Octavio Miguel Rivero-Lezcano
The whole blood model for infection has proven useful to analyze the immunological response to Mycobacterium tuberculosis, because it exerts a significant antimicrobial activity. Although this activity has been generally assumed to be cellular, we have found that the leukocyte fraction of blood from healthy volunteers did not kill the bacilli. We have discovered that plasma was responsible for a large proportion, but not all, of the antimicrobial activity. Furthermore, infected monocytes controlled the mycobacterial multiplication when cultivated in the presence of plasma...
October 2016: Innate Immunity
Christian Chalut
Mycobacteria produce a large variety of surface-exposed lipids with unusual structures. Some of these compounds are ubiquitously present in mycobacteria and play an important role in the structural organization of the cell envelope, while others are species-specific. The biosynthesis of most of these lipids requires modular polyketide synthases (PKS) or non-ribosomal peptide synthetases (NRPS) that are intracellular, suggesting that the assembly of these compounds takes place in the cytosolic compartment or near the inner leaflet of the plasma membrane...
September 2016: Tuberculosis
Chintan H Kapadia, Shaomin Tian, Jillian L Perry, J Christopher Luft, Joseph M DeSimone
Educating our immune system via vaccination is an attractive approach to combat infectious diseases. Eliciting antigen specific cytotoxic T cells (CTLs), CD8(+) effector T cells, is essential in controlling intracellular infectious diseases such as influenza (Flu), tuberculosis (TB), hepatitis, and HIV/AIDS, as well as tumors. However, vaccination utilizing subunit peptides to elicit a potent CD8(+) T cell response with antigenic peptides is typically ineffective due to poor immunogenicity. Here we have engineered a reduction sensitive nanoparticle (NP) based subunit vaccine for intracellular delivery of an antigenic peptide and immunostimulatory adjuvant...
October 3, 2016: Molecular Pharmaceutics
Martin I McLaughlin, Nicholas D Lanz, Peter J Goldman, Kyung-Hoon Lee, Squire J Booker, Catherine L Drennan
Lipoyl synthase (LipA) catalyzes the insertion of two sulfur atoms at the unactivated C6 and C8 positions of a protein-bound octanoyl chain to produce the lipoyl cofactor. To activate its substrate for sulfur insertion, LipA uses a [4Fe-4S] cluster and S-adenosylmethionine (AdoMet) radical chemistry; the remainder of the reaction mechanism, especially the source of the sulfur, has been less clear. One controversial proposal involves the removal of sulfur from a second (auxiliary) [4Fe-4S] cluster on the enzyme, resulting in destruction of the cluster during each round of catalysis...
August 23, 2016: Proceedings of the National Academy of Sciences of the United States of America
Qingguo Meng, Peng Liu, Jian Wang, Yinghui Wang, Libo Hou, Wei Gu, Wen Wang
UNLABELLED: Post-translational modifications such as acetylation are an essential regulatory mechanism of protein function. Spiroplasma eriocheiris, with no cell wall and a helical structure, is a novel pathogen of freshwater crustacean. There is no other evidence of acylation (such as succinylation and propionylation) except acetylation genes in S. eriocheiris concise genome. So the acetylation may play an important role in S. eriocheiris. Here, we conducted the first lysine acetylome in S...
October 4, 2016: Journal of Proteomics
Á Ábrahám, Zs Baranyai, G Gyulai, E Pári, K Horváti, Sz Bősze, É Kiss
Novel peptide conjugates of two antitubercular drug candidates were synthesised and characterised using new tuftsin peptide derivative (OT14) as carrier moiety. As antitubercular drug candidates two pyridopyrimidine derivatives, TB803 (2-allylamino-4-oxopyrido[1,2-a]pyrimidine-3-carbaldehyde) and TB820 (4-oxo-2-(pyrrolidin-1-yl)-pyrido[1,2-a]pyrimidin-3-carbaldehyde) inhibiting vital enzyme of Mycobacterium tuberculosis were applied. Membrane affinity of the compounds TB803 and TB820 and their peptide conjugates was evaluated using experimental lipid mono- and bilayer models...
November 1, 2016: Colloids and Surfaces. B, Biointerfaces
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