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Mtb with host

Rhoo Kun Hyoe, Jacques Robert
Owing to the high incidence of multi-drug resistance and challenges posed by the complex and long duration of treatments, Mycobacterium tuberculosis (Mtb) infections remain a significant clinical burden, which would benefit from development of novel immuno-therapeutic-based treatment strategies. Among early immune effectors, invariant or innate-like (i)T cells are attracting attention because of their potential regulatory activity, which can shape anti-mycobacterial immune responses. Unlike conventional T cells, iT cells express a semi-invariant T cell receptor, and respond rapidly and robustly to molecular patterns presented by MHC class I-like molecules...
December 3, 2018: Developmental and Comparative Immunology
Pramod Kumar Gupta, Savita Kulkarni
Plethora of clinical and scientific information obtained in recent past has strengthened the idea that targeting critical constituents of host immune system may have beneficial outcomes for the treatment of tuberculosis. Macrophages being the primary host for Mycobacterium tuberculosis, offer an attractive target for modulation. Owing to their negligible toxicity, plant derived polysaccharides with the ability to activate macrophages; are suitable candidates for immunomodulation. In the present study, effects of polysaccharide rich extract (PRE) isolated from Tinospora cordifolia, on the survival of intracellular MTB strains and activation of macrophages were investigated...
December 2018: Tuberculosis
Mansi Mehta, Amit Singh
Mycobacterium tuberculosis (Mtb) survives under oxidatively and nitosatively hostile niches inside host phagocytes. In other bacteria, adaptation to these stresses is dependent upon the redox sensitive two component systems (e.g., ArcAB) and transcription factors (e.g., FNR/SoxR). However, these factors are absent in Mtb. Therefore, it is not completely understood how Mtb maintains survival and redox balance in response to reactive oxygen species (ROS) and reactive nitrogen species (RNS). Here, we present evidences that a 4Fe-4S-cofactor containing redox-sensitive transcription factor (WhiB3) is exploited by Mtb to adapt under ROS and RNS stress...
November 27, 2018: Free Radical Biology & Medicine
Wu Li, Wanyan Deng, Jianping Xie
PE/PPE family antigens are distributed mainly in pathogenic mycobacteria and serve as potential antituberculosis (TB) vaccine components. Some PE/PPE family antigens can regulate the host innate immune response, interfere with macrophage activation and phagolysosome fusion, and serve as major sources of antigenic variation. PE/PPE antigens have been associated with mycobacteria pathogenesis; pe/ppe genes are mainly found in pathogenic mycobacteria and are differentially expressed between Mtb and Mycobacterium bovis...
November 27, 2018: Journal of Cellular Physiology
Michael V Tullius, Susana Nava, Marcus A Horwitz
Mycobacterium tuberculosis (Mtb), one of the world's leading causes of death, must acquire nutrients, such as iron, from the host to multiply and cause disease. Iron is an essential metal and Mtb possesses two different systems to acquire iron from its environment: Siderophore-Mediated Iron Acquisition (SMIA) and Heme-Iron Acquisition (HIA), involving uptake and degradation of heme to release ferrous iron. We have discovered that Mycobacterium bovis BCG, the tuberculosis vaccine strain, is severely deficient in HIA, and exploited this phenotypic difference between BCG and Mtb to identify genes involved in HIA by complementing BCG's defect with a fosmid library...
November 19, 2018: Infection and Immunity
Bridgette M Cumming, Kelvin W Addicott, John H Adamson, Adrie Jc Steyn
How Mycobacterium tuberculosis ( Mtb ) rewires macrophage energy metabolism to facilitate survival is poorly characterized. Here, we used extracellular flux analysis to simultaneously measure the rates of glycolysis and respiration in real-time. Mtb infection induced a quiescent energy phenotype in human monocyte-derived macrophages and decelerated flux through glycolysis and the TCA cycle. In contrast, infection with the vaccine strain, M . bovis BCG, or dead Mtb induced glycolytic phenotypes with greater flux...
November 16, 2018: ELife
Maya Gough, Elebeoba May
Mycobacterium tuberculosis (Mtb) is a highly infectious aerosolizable bacterium, which causes upward of 1.5 million deaths per year. Alveolar macrophages, the primary defense cell of the lung, are the preferred host cell of this intracellular bacterium. Vitamin D3 is a known transcription factor, modulating the transcription of pro- and anti-inflammatory cytokines and immunologically relevant proteins. In a vitamin D3 deficient host, the immune systems response to infection is greatly impaired. We used a quantitative systems biology approach to model the impact of long-term vitamin D3 deficiency on macrophage effector response...
July 2018: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Gemma O'Connor, Nitya Krishnan, Aidan Fagan-Murphy, Joseph Cassidy, Seonadh O'Leary, Brian D Robertson, Joseph Keane, Mary P O'Sullivan, Sally-Ann Cryan
Ending the tuberculosis (TB) epidemic by 2030 was recently listed in the United Nations (UN) Sustainable Development Goals alongside HIV/AIDS and malaria as it continues to be a major cause of death worldwide. With a significant proportion of TB cases caused by resistant strains of Mycobacterium tuberculosis (Mtb), there is an urgent need to develop new and innovative approaches to treatment. Since 1989, researchers have been assessing the anti-bacterial effects of the active metabolite of vitamin A, all trans-Retinoic acid (ATRA) solution, in Mtb models...
October 29, 2018: European Journal of Pharmaceutics and Biopharmaceutics
James J Phelan, Sharee A Basdeo, Simone C Tazoll, Sadhbh McGivern, Judit R Saborido, Joseph Keane
Tuberculosis (TB) is the world's biggest infectious disease killer. The increasing prevalence of multidrug-resistant and extensively drug-resistant TB demonstrates that current treatments are inadequate and there is an urgent need for novel therapies. Research is now focused on the development of host-directed therapies (HDTs) which can be used in combination with existing antimicrobials, with a special focus on promoting host defense. Immunometabolic reprogramming is integral to TB host defense, therefore, understanding and supporting the immunometabolic pathways that are altered after infection will be important for the development of new HDTs...
2018: Frontiers in Immunology
Rong Hou, Ravi Nayak, Steven M Pincus, Jinping Lai, Louay M Omran, Samer Al-Kaade, Getahun Abate
Mycobacterium avium-intracellulare complex (MAC) is the most common cause of nontuberculous mycobacterial (NTM) disease in humans. We report a case of esophageal MAC-disease in a patient who had allogeneic bone marrow transplant for acute lymphoblastic leukemia. Although pulmonary MAC in immunocompromised host is not uncommon, there are only a few cases of NTM-associated esophageal mass reported. Our report and literature review highlight the importance of considering MAC in the differential diagnosis of dysphagia or odynophagia...
October 29, 2018: Transplant Infectious Disease: An Official Journal of the Transplantation Society
Xuan Peng, Tao Luo, Xiaoqian Zhai, Chunxi Zhang, Jing Suo, Pengjiao Ma, Chuhan Wang, Lang Bao
Tuberculosis (TB), which is caused by Mycobacterium tuberculosis (Mtb), remains a serious global health problem. The PE/PPE family, featuring unique sequences, structures and expression in Mtb, is reported to interfere with the macrophage response to the pathogen and facilitate its infection. PPE11 (Rv0453) existed in pathogenic mycobacteria and was persistently expressed in the infected guinea pig lungs. However, the role it played in the pathogenesis remains unclear. Here, to investigate the interaction and potential mechanism of PPE11 between pathogens and hosts, we heterologously expressed PPE11 in non-pathogenic, rapidly growing Mycobacterium smegmatis strains...
October 23, 2018: Microbial Pathogenesis
Delia Goletti, Cecilia S Lindestam Arlehamn, Thomas J Scriba, Richard Anthony, Daniela Maria Cirillo, Tonino Alonzi, Claudia M Denkinger, Frank Cobelens
Antibiotic treatment of tuberculosis takes ≥6 months, putting a major burden on patients and health systems in large parts of the world. Treatment beyond 2 months is needed to prevent tuberculosis relapse by clearing remaining, drug-tolerant Mycobacterium tuberculosis bacilli. However, the majority of patients treated for only 2-3 months will cure without relapse and do not need prolonged treatment. Assays that can identify these patients at an early stage of treatment may significantly help reduce the treatment burden, while a test to identify those patients who will fail treatment may help target host-directed therapies...
November 2018: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
Prajna Tripathi, Priyanka Parijat, Virendra Kumar Patel, Janendra K Batra
Mycobacterium tuberculosis ( Mtb ) is known to persist in extremely hostile environments within host macrophages. The ability to withstand such proteotoxic stress comes from its highly conserved molecular chaperone machinery. ClpB, a unique member of the AAA+ family of chaperones, is responsible for resolving aggregates in Mtb and many other bacterial pathogens. Mtb produces two isoforms of ClpB, a full length and an N-terminally truncated form (ClpB∆N), with the latter arising from an internal translation initiation site...
October 2018: FEBS Open Bio
Feng Liu, Jianxia Chen, Peng Wang, Haohao Li, Yilong Zhou, Haipeng Liu, Zhonghua Liu, Ruijuan Zheng, Lin Wang, Hua Yang, Zhenling Cui, Fei Wang, Xiaochen Huang, Jie Wang, Wei Sha, Heping Xiao, Baoxue Ge
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca2+ ) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca2+ transporter CACNA2D3...
October 16, 2018: Nature Communications
Mariateresa Coppola, Tom Hm Ottenhoff
Every day approximately six thousand people die of Tuberculosis (TB). Its causative agent, Mycobacterium tuberculosis (Mtb), is an ancient pathogen that through its evolution developed complex mechanisms to evade immune surveillance and acquire the ability to establish persistent infection in its hosts. Currently, it is estimated that one-fourth of the human population is latently infected with Mtb and among those infected 3-10% are at risk of developing active TB disease during their lifetime. The currently available diagnostics are not able to detect this risk group for prophylactic treatment to prevent transmission...
July 7, 2018: Seminars in Immunology
Anjana Radhakrishnan, Christopher M Furze, Mohd Syed Ahangar, Elizabeth Fullam
One of the major obstacles to obtaining a complete structural and functional understanding of proteins encoded by the Mycobacterium tuberculosis ( Mtb ) pathogen is due to significant difficulties in producing recombinant mycobacterial proteins. Recent advances that have utilised the closely related Mycobacterium smegmatis species as a native host have been effective. Here we have developed a method for the rapid screening of both protein production and purification strategies of mycobacterial proteins in whole M...
September 27, 2018: RSC Advances
Katharina Ronacher, Roma Sinha, Michelle Cestari
Approximately 10% of individuals latently infected with Mycobacterium tuberculosis (Mtb) develop active tuberculosis (TB) during their lifetime. Although it is well recognized that T-helper 1 immune responses are crucial for containing latent TB infection, the full array of host factors conferring protective immunity from TB progression are not completely understood. IL-22 is produced by cells of the innate and adaptive immune system including innate lymphoid cells, and natural killer cells as well as T lymphocytes (Th1, Th17, and Th22) and binds to its cognate receptor, the IL-22R1, which is expressed on non-hematopoietic cells such as lung epithelial cells...
2018: Frontiers in Immunology
Emily S C Rittershaus, Seung-Hun Baek, Inna V Krieger, Samantha J Nelson, Yu-Shan Cheng, Subhalaxmi Nambi, Richard E Baker, John D Leszyk, Scott A Shaffer, James C Sacchettini, Christopher M Sassetti
Upon inhibition of respiration, which occurs in hypoxic or nitric oxide-containing host microenvironments, Mycobacterium tuberculosis (Mtb) adopts a non-replicating "quiescent" state and becomes relatively unresponsive to antibiotic treatment. We used comprehensive mutant fitness analysis to identify regulatory and metabolic pathways that are essential for the survival of quiescent Mtb. This genetic study identified a protein acetyltransferase (Mt-Pat/Rv0998) that promoted survival and altered the flux of carbon from oxidative to reductive tricarboxylic acid (TCA) reactions...
October 4, 2018: Cell Chemical Biology
Ruchi Paroha, Shivendra K Chaurasiya, Rashmi Chourasia
Mycobacterium tuberculosis (Mtb) infects millions of people each year. These bacilli can survive inside macrophages. To favor their survival, pathogen alters various signal transduction pathways in host cells. Phospholipase C (PLC) signaling regulates various processes in mammalian cells but has never been investigated for their roles in regulating phagocytosis and killing of mycobacteria by macrophages. Here, we report that infection with Mtb but not Mycobacterium smegmatis (MS) induces phosphorylation of PLC-γ2 at tyrosine 1217 in J774A...
October 14, 2018: Journal of Cellular Biochemistry
Anthony M Cadena, Yixuan Ma, Tao Ding, MacKenzie Bryant, Pauline Maiello, Adam Geber, Philana Ling Lin, JoAnne L Flynn, Elodie Ghedin
BACKGROUND: The specific interactions of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), and the lung microbiota in infection are entirely unexplored. Studies in cancer and other infectious diseases suggest that there are important exchanges occurring between host and microbiota that influence the immunological landscape. This can result in alterations in immune regulation and inflammation both locally and systemically. To assess whether Mtb infection modifies the lung microbiome, and identify changes in microbial abundance and diversity as a function of pulmonary inflammation, we compared infected and uninfected lung lobe washes collected serially from 26 macaques by bronchoalveolar lavage over the course of infection...
October 9, 2018: Microbiome
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