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secretory system in tb

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...
November 21, 2014: 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
Maria H Daleke-Schermerhorn, Tristan Felix, Zora Soprova, Corinne M Ten Hagen-Jongman, David Vikström, Laleh Majlessi, Joep Beskers, Frank Follmann, Karin de Punder, Nicole N van der Wel, Thomas Baumgarten, Thang V Pham, Sander R Piersma, Connie R Jiménez, Peter van Ulsen, Jan-Willem de Gier, Claude Leclerc, Wouter S P Jong, Joen Luirink
Outer membrane vesicles (OMVs) are spherical nanoparticles that naturally shed from Gram-negative bacteria. They are rich in immunostimulatory proteins and lipopolysaccharide but do not replicate, which increases their safety profile and renders them attractive vaccine vectors. By packaging foreign polypeptides in OMVs, specific immune responses can be raised toward heterologous antigens in the context of an intrinsic adjuvant. Antigens exposed at the vesicle surface have been suggested to elicit protection superior to that from antigens concealed inside OMVs, but hitherto robust methods for targeting heterologous proteins to the OMV surface have been lacking...
September 2014: Applied and Environmental Microbiology
Talia L Ramsdell, Laura A Huppert, Tatyana A Sysoeva, Sarah M Fortune, Briana M Burton
Among protein secretion systems, there are specialized ATPases that serve different functions such as substrate recognition, substrate unfolding, and assembly of the secretory machinery. ESX (early secretory antigen target 6 kDa secretion) protein secretion systems require FtsK/SpoIIIE family ATPases but the specific function of these ATPases is poorly understood. The ATPases of ESX secretion systems have a unique domain architecture among proteins of the FtsK/SpoIIIE family. All well-studied FtsK family ATPases to date have one ATPase domain and oligomerize to form a functional molecular machine, most commonly a hexameric ring...
March 13, 2015: Journal of Molecular Biology
Luis Solans, Nacho Aguiló, Sofía Samper, Alexandre Pawlik, Wafa Frigui, Carlos Martín, Roland Brosch, Jesús Gonzalo-Asensio
The ESX-1 secreted virulence factor ESAT-6 is one of the major and most well-studied virulence factors of Mycobacterium tuberculosis, given that its inactivation severely attenuates virulent mycobacteria. In this work, we show that clinical isolates of M. tuberculosis produce and secrete larger amounts of ESAT-6 than the widely used M. tuberculosis H37Rv laboratory strain. A search for the genetic polymorphisms underlying this observation showed that whiB6 (rv3862c), a gene upstream of the ESX-1 genetic locus that has not previously been found to be implicated in the regulation of the ESX-1 secretory apparatus, presents a unique single nucleotide insertion in its promoter region in strains H37Rv and H37Ra...
August 2014: Infection and Immunity
V A Shkurupiy, L B Kim, O V Potapova, L A Cherdantseva, A N Putyatina, I K Nikonova
The study in mouse model of BCG-induced granulomatous inflammation showed that early pulmonary fibrosis (day 3-30 postinfection) in tuberculous inflammation was primarily determined by increased number of fibroblasts in the lung interstitium and granulomas and enhanced fibroplastic activity. Fibroplastic processes are initiated via an increase in secretory activity of activated granuloma macrophages caused by the persistence of the pathogen in the cells of the mononuclear phagocytic system. The dynamics of hydroxyproline concentration under these conditions is determined by changes in the number and differentiation degree of fibroblasts in granulomas and lung interstitium at various stages of tuberculous inflammation...
April 2014: Bulletin of Experimental Biology and Medicine
Qingfeng Liu, Chi Zhang, Xiaoyao Zheng, Xiayan Shao, Xi Zhang, Qizhi Zhang, Xinguo Jiang
The frequent outbreak of respiratory infectious diseases such as influenza and pulmonary tuberculosis calls for new immunization strategies with high effectiveness. Nasal immunization is one of the most potential methods to prevent the diseases infected through the respiratory tract. In this study, we designed a water-soluble system based on antigen/N-trimethylaminoethylmethacrylate chitosan conjugates for nasal immunization. N-trimethylaminoethylmethacrylate chitosan (TMC) was synthesized by free radical polymerization of chitosan and N-trimethylaminoethylmethacrylate chloride and identified by (1)H NMR and FT-IR...
May 7, 2014: Vaccine
Asani Bhaduri, Richa Misra, Abhijit Maji, Preetida J Bhetaria, Sonakshi Mishra, Gunjan Arora, Lalit Kumar Singh, Neha Dhasmana, Neha Dubey, Jugsharan Singh Virdi, Yogendra Singh
Cyclophilins are prolyl isomerases with multitude of functions in different cellular processes and pathological conditions. Cyclophilin A (PpiA) of Mycobacterium tuberculosis is secreted during infection in intraphagosomal niche. However, our understanding about the evolutionary origin, secretory mechanism or the interactome of M. tuberculosis PpiA is limited. This study demonstrates through phylogenetic and structural analyses that PpiA has more proximity to human cyclophilins than the prokaryotic counterparts...
2014: PloS One
Weiwei Liu, Yuan Peng, Yanlin Yin, Zhihui Zhou, Wanding Zhou, Yalei Dai
The 6-kDa early secretory antigenic target (ESAT-6) of Mycobacterium tuberculosis is strongly correlated with subversion of innate immune responses against invading mycobacteria. To understand the role of ESAT-6 in macrophage response against M. tuberculosis, the effects of ESAT-6 on macrophage generation of reactive oxygen species (ROS) and production of cytokines were studied. ESAT-6-induced macrophage secretion of monocyte chemoattractant protein-1 and TNF-α was found in a time- and dose-dependent manner...
June 2014: Inflammation
Niels Peter H Knudsen, Sara Nørskov-Lauritsen, Gregory M Dolganov, Gary K Schoolnik, Thomas Lindenstrøm, Peter Andersen, Else Marie Agger, Claus Aagaard
A central goal in vaccine research is the identification of relevant antigens. The Mycobacterium tuberculosis chromosome encodes 23 early secretory antigenic target (ESAT-6) family members that mostly are localized as gene pairs. In proximity to five of the gene pairs are ESX secretion systems involved in the secretion of the ESAT-6 family proteins. Here, we performed a detailed and systematic investigation of the vaccine potential of five possible Esx dimer substrates, one for each of the five ESX systems...
January 21, 2014: Proceedings of the National Academy of Sciences of the United States of America
Seiji Shibasaki, Wataru Aoki, Mitsuyoshi Ueda
Medical facilities and advances in therapeutics have improved world over in recent times. Concomitant with this, the human population has been growing steadily. However, emerging infectious diseases such as severe acute respiratory syndrome (SARS) and AIDS, as well as re-emerging infectious diseases such as Japanese encephalitis and dengue fever, have been spreading in recent times. Three major infectious diseases, namely AIDS, malaria, and tuberculosis, are killing around 8 million people in the world annually...
2013: Yakugaku Zasshi: Journal of the Pharmaceutical Society of Japan
Shabir Ahmad Mir, Sadhna Sharma
Bacterial protein synthesis initiates with a formyl-methionine group. Addition of the antibiotic actinonin, a known peptide deformylase inhibitor, at the time of induction of protein expression results in the retention of the formyl group by the overexpressed protein. We have demonstrated the application of this system to obtain N-formylated form of a mycobacterial secretory protein ESAT-6 which is an important target for T-cell recognition during Mycobacterium tuberculosis infection. The gene encoding the ESAT-6 of M...
December 2013: Protein Expression and Purification
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