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secretory system in tb

Nina Chatterjee, Rupal Ojha, Nazia Khatoon, Vijay Kumar Prajapati
Tuberculosis is a menacing disease caused eminently to the people inhabiting the tropical and sub-tropical nations. A holistic approach is required to generate T and B memory cells to effectuate a long-term exemption from the pulmonary tuberculosis. In this study, immunoinformatic approaches were used to design a multi-epitope-based subunit vaccine for pulmonary tuberculosis which may improve human immune system. The various B-cell, TH cell and TC cell binding epitopes were predicted for selected 2 membrane and 12 secretory proteins of Mycobacterium tuberculosis...
June 16, 2018: International Journal of Biological Macromolecules
Mariona Camps-Bossacoma, Francisco J Pérez-Cano, Àngels Franch, Margarida Castell
Background: A 10% cocoa-enriched diet influences immune system functionality including the prevention of the antibody response and the induction of lower immunoglobulin (Ig) concentrations. However, neither cocoa polyphenols nor cocoa fiber can totally explain these immunoregulatory properties. Objectives: This study aimed to establish the influence of cocoa theobromine in systemic and intestinal Ig concentrations and to determine the effect of cocoa or theobromine feeding on lymphoid tissue lymphocyte composition...
March 1, 2018: Journal of Nutrition
Takahiro Ushigusa, Yoshiyuki Koyama, Tomoko Ito, Kenichi Watanabe, James K Chambers, Aya Hasegawa, Kazuyuki Uchida, Ryoji Kanegi, Shingo Hatoya, Toshio Inaba, Kikuya Sugiura
By using a complex of DNA, polyethylenimine and chondroitin sulfate, the in vivo transfection of early secretory antigenic target-6 (ESAT-6) gene into tumor cells was found to cause significant suppression of the tumor growth. In order to apply the method in clinical cancer treatment in dogs and cats, mechanisms underlying the suppressive effects were investigated in a tumor-bearing mouse model. The transfection efficiency was only about 10%, but the transfection of ESAT-6 DNA nevertheless induced systemic immune responses against ESAT-6...
February 9, 2018: Journal of Veterinary Medical Science
Ah-Ra Jang, Joo-Hee Choi, Sung Jae Shin, Jong-Hwan Park
Mycobacterium tuberculosis is a highly virulent bacterium that causes tuberculosis. It infects about one third of the world's population. Type I interferons (IFNs) play a detrimental role in host defense against M. tuberculosis infection. Proteins secreted by M. tuberculosis through ESX-1 secretion system contribute to type I IFNs production. However, the precise mechanism by which 6-kDa early secretory antigen target (ESAT6), one of ESX-1-mediated secretory proteins, induces type I IFNs production in host cells is currently unclear...
April 2018: Cytokine
Yanina R Sevastsyanovich, David R Withers, Claire L Marriott, Faye C Morris, Timothy J Wells, Douglas F Browning, Irene Beriotto, Ewan Ross, Hossam Omar Ali, Catherine A Wardius, Adam F Cunningham, Ian R Henderson, Amanda E Rossiter
The use of recombinant attenuated Salmonella vaccine (RASV) strains is a promising strategy for presenting heterologous antigens to the mammalian immune system to induce both cellular and humoral immune responses. However, studies on RASV development differ on where heterologous antigens are expressed and localized within the bacterium, and it is unclear how antigen localization modulates the immune response. Previously, we exploited the plasmid-encoded toxin (Pet) autotransporter system for accumulation of heterologous antigens in cell culture supernatant...
December 2017: Infection and Immunity
D F Hoft, M Xia, G L Zhang, A Blazevic, J Tennant, C Kaplan, G Matuschak, T J Dube, H Hill, L S Schlesinger, P L Andersen, V Brusic
Protective efficacy of Bacillus Calmette-Guérin (BCG) may be affected by the methods and routes of vaccine administration. We have studied the safety and immunogenicity of oral (PO) and/or intradermal (ID) administration of BCG in healthy human subjects. No major safety concerns were detected in the 68 healthy adults vaccinated with PO and/or ID BCG. Although both PO and ID BCG could induce systemic Th1 responses capable of IFN-γ production, ID BCG more strongly induced systemic Th1 responses. In contrast, stronger mucosal responses (TB-specific secretory IgA and bronchoalveolar lavage T cells) were induced by PO BCG vaccination...
March 2018: Mucosal Immunology
Shahrzad Ahangarzadeh, Mojgan Bandehpour, Bahram Kazemi
OBJECTIVES: Tuberculosis (TB) is still one of the problematic infectious diseases in developing countries, especially in Iran. In the present study, we applied ribosome display technique to select single chain variable fragments (scFvs) specific for the 6-kDa early secretory antigenic target (ESAT-6) antigen of Mycobacterium tuberculosis from a mouse scFv library. MATERIALS AND METHODS: The gene encoding ESAT-6 was cloned into pET22b(+) plasmid and expressed in Escherichia coli BL21 (DE3)...
March 2017: Iranian Journal of Basic Medical Sciences
William H Conrad, Morwan M Osman, Jonathan K Shanahan, Frances Chu, Kevin K Takaki, James Cameron, Digby Hopkinson-Woolley, Roland Brosch, Lalita Ramakrishnan
Mycobacterium tuberculosis and Mycobacterium marinum are thought to exert virulence, in part, through their ability to lyse host cell membranes. The type VII secretion system ESX-1 [6-kDa early secretory antigenic target (ESAT-6) secretion system 1] is required for both virulence and host cell membrane lysis. Both activities are attributed to the pore-forming activity of the ESX-1-secreted substrate ESAT-6 because multiple studies have reported that recombinant ESAT-6 lyses eukaryotic membranes. We too find ESX-1 of M...
February 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
Jacques Augenstreich, Ainhoa Arbues, Roxane Simeone, Evert Haanappel, Alice Wegener, Fadel Sayes, Fabien Le Chevalier, Christian Chalut, Wladimir Malaga, Christophe Guilhot, Roland Brosch, Catherine Astarie-Dequeker
Although phthiocerol dimycocerosates (DIM) are major virulence factors of Mycobacterium tuberculosis (Mtb), the causative agent of human tuberculosis, little is known about their mechanism of action. Localized in the outer membrane of mycobacterial pathogens, DIM are predicted to interact with host cell membranes. Interaction with eukaryotic membranes is a property shared with another virulence factor of Mtb, the early secretory antigenic target EsxA (also known as ESAT-6). This small protein, which is secreted by the type VII secretion system ESX-1 (T7SS/ESX-1), is involved in phagosomal rupture and cell death induced by virulent mycobacteria inside host phagocytes...
July 2017: Cellular Microbiology
Isaac D Otchere, Simon R Harris, Sanches L Busso, Adwoa Asante-Poku, Stephen Osei-Wusu, Kwadwo Koram, Julian Parkhill, Sebastien Gagneux, Dorothy Yeboah-Manu
OBJECTIVE/BACKGROUND: Mycobacterium africanum (MAF) remains an important TB causing pathogen in West Africa; however, little is known about its population structure and actual diversity which may have implications for diagnostics and vaccines. We carried out comparative genomics analysis of candidate Mycobacterium tuberculosis (MTB) and MAF using whole genome sequencing. METHODS: Clinical MTB complex strains (n=187) comprising L4 (n=22), L5 (n=126), and L6 (n=39) isolated over 8years from Ghana were whole genome sequenced...
December 2016: International Journal of Mycobacteriology
Matthias I Gröschel, Fadel Sayes, Roxane Simeone, Laleh Majlessi, Roland Brosch
Mycobacterium tuberculosis uses sophisticated secretion systems, named 6 kDa early secretory antigenic target (ESAT6) protein family secretion (ESX) systems (also known as type VII secretion systems), to export a set of effector proteins that helps the pathogen to resist or evade the host immune response. Since the discovery of the esx loci during the M. tuberculosis H37Rv genome project, structural biology, cell biology and evolutionary analyses have advanced our knowledge of the function of these systems...
November 2016: Nature Reviews. Microbiology
Huan Yang, Hua Tang, Xin-Xin Chen, Chang-Jian Zhang, Pan-Pan Zhu, Hui Ding, Wei Chen, Hao Lin
Tuberculosis is killing millions of lives every year and on the blacklist of the most appalling public health problems. Recent findings suggest that secretory protein of Mycobacterium tuberculosis may serve the purpose of developing specific vaccines and drugs due to their antigenicity. Responding to global infectious disease, we focused on the identification of secretory proteins in Mycobacterium tuberculosis. A novel method called MycoSec was designed by incorporating g-gap dipeptide compositions into pseudo amino acid composition...
2016: BioMed Research International
Stephanie Swanson, Thomas R Ioerger, Nathan W Rigel, Brittany K Miller, Miriam Braunstein, James C Sacchettini
UNLABELLED: While SecA is the ATPase component of the major bacterial secretory (Sec) system, mycobacteria and some Gram-positive pathogens have a second paralog, SecA2. In bacteria with two SecA paralogs, each SecA is functionally distinct, and they cannot compensate for one another. Compared to SecA1, SecA2 exports a distinct and smaller set of substrates, some of which have roles in virulence. In the mycobacterial system, some SecA2-dependent substrates lack a signal peptide, while others contain a signal peptide but possess features in the mature protein that necessitate a role for SecA2 in their export...
February 2016: Journal of Bacteriology
Michael Allen, Cedric Bailey, Ian Cahatol, Levi Dodge, Jay Yim, Christine Kassissa, Jennifer Luong, Sarah Kasko, Shalin Pandya, Vishwanath Venketaraman
Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tb), continues to be one of the most prevalent infectious diseases in the world. There is an upward trend in occurrence due to emerging multidrug resistant strains and an increasingly larger proportion of immunocompromised patient populations as a result of the acquired immunodeficiency syndrome pandemic. The complex and often deadly combination of multidrug resistant M. tb (MDR-M. tb) along with human immunodeficiency virus (HIV) puts a significant number of people at high risk for pulmonary and extra-pulmonary TB without sufficient therapeutic options available...
2015: Frontiers in Immunology
Yoshiyuki Koyama, Chieko Yoshihara, Tomoko Ito
Immune escape of tumor cells is one of the main obstacles hindering the effectiveness of cancer immunotherapy. We developed a novel strategy to block immune escape by transfecting tumor cells in vivo with genes of pathogenic antigens from Mycobacterium tuberculosis (TB). This induces presentation of the TB antigen on tumor cell surfaces, which can be recognized by antigen presenting cells (APCs) as a "danger signal" to stimulate antitumor immune response. This strategy is also expected to amplify the immune response against tumor-associated antigens, and block immune escape of the tumor...
2015: Pharmaceutics
Jun L Xue, Ling Yi, Zhou H Yan, Xin Li, Xiao J Wang, Pang J Wei, Jiao E Zeng, Yan L Zhao, Hong T Zhang
SPLUNC1 (Short palate, lung and nasal epithelium clone1) protein is an abundant secretory product of epithelia present throughout the conducting airways. Although its function is still not fully known, most studies have focused on its defensive effect in the infection of human airways and its potential to serve as a molecular marker for lung cancer. In this study, we further evaluated the SPLUNC1 expression in patients with lung disease to explore its role in cancer or tuberculosis at the protein level. We generated a panel of antibodies by using protein from a eukaryotic expression system as the immunogen to mice...
June 2015: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
DanDan Huang, Lang Bao
BACKGROUND: Mycobacterium tuberculosis (Mtb) persists within immature phagosomes by preventing their maturation into phagolysosomes. Although the early secretory antigenic target 6 (ESAT-6) system 1 (ESX-1) secretion-associated protein B (EspB) of Mtb is strongly linked to immunogenicity and virulence of this organism, its mechanism of action remains largely unclear. This study aimed to investigate EspB effects on autophagy in murine ANA-1 macrophage cells. METHODS: EspB gene was amplified by polymerase chain reaction from Mtb H37Rv genomic DNA to express recombinant EspB protein...
December 2016: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
Vanessa Bastos Pereira, Tessália Diniz Luerce Saraiva, Bianca Mendes Souza, Meritxell Zurita-Turk, Marcela Santiago Pacheco Azevedo, Camila Prósperi De Castro, Pamela Mancha-Agresti, Janete Soares Coelho Dos Santos, Ana Cristina Gomes Santos, Ana Maria Caetano Faria, Sophie Leclercq, Vasco Azevedo, Anderson Miyoshi
The use of the food-grade bacterium Lactococcus lactis as a vehicle for the oral delivery of DNA vaccine plasmids constitutes a promising strategy for vaccination. The delivery of DNA plasmids into eukaryotic cells is of critical importance for subsequent DNA expression and effectiveness of the vaccine. In this context, the use of the recombinant invasive L. lactis FnBPA+ (fibronectin-binding protein A) strain for the oral delivery of the eukaryotic expression vector vaccination using lactic acid bacteria (pValac), coding for the 6-kDa early secreted antigenic target (ESAT-6) gene of Mycobacterium tuberculosis, could represent a new DNA vaccine strategy against tuberculosis...
February 2015: Applied Microbiology and Biotechnology
Damian C Ekiert, Jeffery S Cox
Nearly 10% of the coding capacity of the Mycobacterium tuberculosis genome is devoted to two highly expanded and enigmatic protein families called PE and PPE, some of which are important virulence/immunogenicity factors and are secreted during infection via a unique alternative secretory system termed "type VII." How PE-PPE proteins function during infection and how they are translocated to the bacterial surface through the five distinct type VII secretion systems [ESAT-6 secretion system (ESX)] of M. tuberculosis is poorly understood...
October 14, 2014: Proceedings of the National Academy of Sciences of the United States of America
Taha Roodbar Shojaei, Mohamad Amran Mohd Salleh, Meisam Tabatabaei, Alireza Ekrami, Roya Motallebi, Tavoos Rahmani-Cherati, Abdollah Hajalilou, Raheleh Jorfi
Mycobacterium tuberculosis, the causing agent of tuberculosis, comes second only after HIV on the list of infectious agents slaughtering many worldwide. Due to the limitations behind the conventional detection methods, it is therefore critical to develop new sensitive sensing systems capable of quick detection of the infectious agent. In the present study, the surface modified cadmium-telluride quantum dots and gold nanoparticles conjunct with two specific oligonucleotides against early secretory antigenic target 6 were used to develop a sandwich-form fluorescence resonance energy transfer-based biosensor to detect M...
November 2014: Brazilian Journal of Infectious Diseases
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