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https://www.readbyqxmd.com/read/27935825/microglia-activation-in-a-pediatric-rabbit-model-of-tuberculous-meningitis
#1
Elizabeth W Tucker, Supriya Pokkali, Zhi Zhang, Vincent P DeMarco, Mariah Klunk, Elizabeth S Smith, Alvaro A Ordonez, Marie-France Penet, Zaver Bhujwalla, Sanjay K Jain, Sujatha Kannan
Central nervous system (CNS) tuberculosis (TB) is the most severe form of extra-pulmonary TB and disproportionately affects young children where the developing brain has a unique host response. New Zealand white rabbits were infected with Mycobacterium tuberculosis via subarachnoid inoculation at postnatal day 4-8 and evaluated until 4-6 weeks post-infection. Control and infected rabbit kits were assessed for the development of neurological deficits, bacterial burden, and postmortem microbiologic and pathologic changes...
December 1, 2016: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/27931677/assuming-the-role-of-mitochondria-in-mycobacterial-infection
#2
REVIEW
Rikesh K Dubey
Tuberculosis is one of the leading causes of death by Mycobacterium tuberculosis (Mtb) affecting millions of people worldwide. Mycobacterium species enter host macrophages during infection and target various cellular organelles and their function for their own benefit. Mitochondria appear to be among the important targets for bacterial pathogens. Mtb and other pathogenic bacteria secrete various proteins that initiate structural changes in mitochondria to modulate its function. Additionally, virulent mycobacteria interfere with the balance between pro- and anti-apoptotic factors to inhibit apoptosis and, in later stages, promote necrosis...
December 2016: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/27924827/pd-1-pd-l-pathway-inhibits-m-tb-specific-cd4-t-cell-functions-and-phagocytosis-of-macrophages-in-active-tuberculosis
#3
Lei Shen, Yan Gao, Yuanyuan Liu, Bingyan Zhang, Qianqian Liu, Jing Wu, Lin Fan, Qinfang Ou, Wenhong Zhang, Lingyun Shao
The role of the PD-1/PD-L pathway in a murine model of tuberculosis remains controversial regarding viral infections and clinical tuberculosis. We conducted a case-control study to investigate the modulating role and mechanism of the PD-1/PD-L pathway in patients with active tuberculosis. Fifty-nine participants, including 43 active tuberculosis (ATB) patients and 16 healthy controls (HC), were enrolled. Cell surface staining and flow cytometry were used to detect the expressions of PD-1 and its ligands on T cells and monocytes...
December 7, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27918526/mycobacterium-tuberculosis-esxh-inhibits-escrt-dependent-cd4-t-cell-activation
#4
Cynthia Portal-Celhay, JoAnn M Tufariello, Smita Srivastava, Aleena Zahra, Thais Klevorn, Patricia S Grace, Alka Mehra, Heidi S Park, Joel D Ernst, William R Jacobs, Jennifer A Philips
Mycobacterium tuberculosis (Mtb) establishes a persistent infection, despite inducing antigen-specific T-cell responses. Although T cells arrive at the site of infection, they do not provide sterilizing immunity. The molecular basis of how Mtb impairs T-cell function is not clear. Mtb has been reported to block major histocompatibility complex class II (MHC-II) antigen presentation; however, no bacterial effector or host-cell target mediating this effect has been identified. We recently found that Mtb EsxH, which is secreted by the Esx-3 type VII secretion system, directly inhibits the endosomal sorting complex required for transport (ESCRT) machinery...
December 5, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27917833/crystal-structure-of-the-toxin-msmeg_6760-the-structural-homolog-of-mycobacterium-tuberculosis-rv2035-a-novel-type-ii-toxin-involved-in-the-hypoxic-response
#5
R Alexandra Bajaj, Mark A Arbing, Annie Shin, Duilio Cascio, Linda Miallau
The structure of Msmeg_6760, a protein of unknown function, has been determined. Biochemical and bioinformatics analyses determined that Msmeg_6760 interacts with a protein encoded in the same operon, Msmeg_6762, and predicted that the operon is a toxin-antitoxin (TA) system. Structural comparison of Msmeg_6760 with proteins of known function suggests that Msmeg_6760 binds a hydrophobic ligand in a buried cavity lined by large hydrophobic residues. Access to this cavity could be controlled by a gate-latch mechanism...
December 1, 2016: Acta Crystallographica. Section F, Structural Biology Communications
https://www.readbyqxmd.com/read/27917375/recombinant-lipoprotein-rv1016c-derived-from-mycobacterium-tuberculosis-is-a-tlr-2-ligand-that-induces-macrophages-apoptosis-and-inhibits-mhc-ii-antigen-processing
#6
Haibo Su, Shenglin Zhu, Lin Zhu, Wei Huang, Honghai Wang, Zhi Zhang, Ying Xu
TLR2-dependent cellular signaling in Mycobacterium tuberculosis-infected macrophages causes apoptosis and inhibits class II major histocompatibility complex (MHC-II) molecules antigen processing, leading to evasion of surveillance. Mycobacterium tuberculosis (MTB) lipoproteins are an important class of Toll-like receptor (TLR) ligand, and identified as specific components that mediate these effects. In this study, we identified and characterized MTB lipoprotein Rv1016c (lpqT) as a cell wall associated-protein that was exposed on the cell surface and enhanced the survival of recombinants M...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27914363/new-insights-into-the-sar-and-drug-combination-synergy-of-2-quinolin-4-yloxy-acetamides-against-mycobacterium-tuberculosis
#7
Bruno Couto Giacobbo, Kenia Pissinate, Valnês Rodrigues-Junior, Anne Drumond Villela, Estêvão Silveira Grams, Bruno Lopes Abbadi, Fernanda Teixeira Subtil, Nathalia Sperotto, Rogério Valim Trindade, Davi Fernando Back, Maria Martha Campos, Luiz Augusto Basso, Pablo Machado, Diógenes Santiago Santos
2-(Quinolin-4-yloxy)acetamides have been described as potent and selective in vitro inhibitors of Mycobacterium tuberculosis (Mtb) growth. Herein, a new series of optimized compounds were found to demonstrate highly potent antitubercular activity, with minimum inhibitory concentration (MIC) values against drug-susceptible and drug-resistant Mycobacterium tuberculosis strains in the submicromolar range. Furthermore, the most active compounds had no apparent toxicity to mammalian cells, and they showed intracellular activities similar to those of isoniazid and rifampin in a macrophage model of Mtb infection...
November 23, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27914088/murine-mycobacterium-marinum-infection-as-a-model-for-tuberculosis
#8
Julia Lienard, Fredric Carlsson
Mycobacteria are a major human health problem globally. Regarding tuberculosis the situation is worsened by the poor efficacy of current vaccine regimens and by emergence of drug-resistant strains (Manjelievskaia J et al, Trans R Soc Trop Med Hyg 110: 110, 2016; Pereira et al., Lancet Infect Dis 12:300-306, 2012; http://www.who.int/tb/publications/global_report/en/) undermining both disease-prevention and available treatments. Thus, increased basic understanding of mycobacterial-and particularly Mycobacterium tuberculosis-virulence strategies and pathogenesis is of great importance...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27913648/cd36-mediated-uptake-of-surfactant-lipids-by-human-macrophages-promotes-intracellular-growth-of-mycobacterium-tuberculosis
#9
Claire E Dodd, Charlie J Pyle, Rebecca Glowinski, Murugesan V S Rajaram, Larry S Schlesinger
Mycobacterium tuberculosis imposes a large global health burden as the airborne agent of tuberculosis. Mycobacterium tuberculosis has been flourishing in human populations for millennia and is therefore highly adapted to the lung environment. Alveolar macrophages, a major host cell niche for M. tuberculosis, are not only phagocytose inhaled microbes and particulate matter but are also crucial in catabolizing lung surfactant, a lipid-protein complex that lines the alveolar spaces. Because macrophage host defense properties can be regulated by surfactant and M...
December 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27908271/host-directed-therapeutics-against-mycobacterial-infections
#10
Haruaki Tomioka, Chiaki Sano, Yutaka Tatano
The high incidence of tuberculosis (TB) in the world, especially in developing countries, the resurgence of TB in industrialized countries, and the global increase in the prevalence of Mycobacterium avium complex infections in immunocompromised hosts have prompted the quest for novel antimycobacterial drugs. However, the development of such antimicrobial chemotherapeutics is currently making very slow progress even with using the bioinformatics-based methodology for drug design. It thus appears that devising improved administration protocols for clinical treatment against intractable mycobacterial infections using existing chemotherapeutics is more practical than awaiting the development of new antimycobacterial drugs...
December 2, 2016: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/27902779/differential-cytokine-gene-expression-in-granulomas-from-lungs-and-lymph-nodes-of-cattle-experimentally-infected-with-aerosolized-mycobacterium-bovis
#11
Mitchell V Palmer, Tyler C Thacker, W Ray Waters
The hallmark lesion of tuberculosis in humans and animals is the granuloma. The granuloma represents a distinct host cellular immune response composed of epithelioid macrophages, lymphocytes, and multinucleated giant cells, often surrounding a caseous necrotic core. Within the granuloma, host-pathogen interactions determine disease outcome. Factors within the granulomas such as cytokines and chemokines drive cell recruitment, activity, function and ultimately the success or failure of the host's ability to control infection...
2016: PloS One
https://www.readbyqxmd.com/read/27901051/mycobacterium-avium-mav2054-protein-induces-macrophage-apoptosis-by-targeting-mitochondria-and-reduces-intracellular-bacterial-growth
#12
Kang-In Lee, Jake Whang, Han-Gyu Choi, Yeo-Jin Son, Haet Sal Jeon, Yong Woo Back, Hye-Soo Park, Seungwha Paik, Jeong-Kyu Park, Chul Hee Choi, Hwa-Jung Kim
Mycobacterium avium complex induces macrophage apoptosis. However, the M. avium components that inhibit or trigger apoptosis and their regulating mechanisms remain unclear. We recently identified the immunodominant MAV2054 protein by fractionating M. avium culture filtrate protein by multistep chromatography; this protein showed strong immuno-reactivity in M. avium complex pulmonary disease and in patients with tuberculosis. Here, we investigated the biological effects of MAV2054 on murine macrophages. Recombinant MAV2054 induced caspase-dependent macrophage apoptosis...
November 30, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27897233/changes-in-the-membrane-associated-proteins-of-exosomes-released-from-human-macrophages-after-mycobacterium-tuberculosis-infection
#13
Gustavo Diaz, Lisa M Wolfe, Nicole A Kruh-Garcia, Karen M Dobos
Tuberculosis (TB) is the deadliest infectious disease worldwide. One obstacle hindering the elimination of TB is our lack of understanding of host-pathogen interactions. Exosomes, naturally loaded with microbial molecules, are circulating markers of TB. Changes in the host protein composition of exosomes from Mycobacterium tuberculosis (Mtb)-infected cells have not been described, can contribute to our understanding of the disease process, and serve as a direct source of biomarkers or as capture targets to enrich for exosomes containing microbial molecules...
November 29, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27892584/a-short-history-of-phototherapy-vitamin-d-and-skin-disease
#14
Paul Jarrett, Robert Scragg
The earliest record between sun exposure and skin disease goes back five millennia to the ancient Egyptians. The modern scientific era of medical light therapy and skin diseases started in 1877 when Downs and Blunt reported that exposure to light inhibited fungal growth in test tubes. Continuing research generated a growing medical interest in the potential the effects of light to treat and cure skin diseases considered as parasitic. This culminated in the awarding of the 1903 Nobel Prize in Medicine to Niels Finsen for his pioneering work showing that light could successfully treat cutaneous mycobacterium tuberculosis (lupus vulgaris), a disfiguring disorder common at the time...
November 28, 2016: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/27891500/interspecies-communication-between-pathogens-and-immune-cells-via-bacterial-membrane-vesicles
#15
Katerina S Jurkoshek, Ying Wang, Jaffre J Athman, Marian R Barton, Pamela A Wearsch
The production of extracellular vesicles is a universal mechanism for intercellular communication that is conserved across kingdoms. Prokaryotes secrete 50-250 nm membrane vesicles (MVs) in a manner that is regulated by environmental stress and is thought to promote survival. Since many types of host-derived stress are encountered during infection, this implies an important role for MV secretion in bacterial pathogenesis. Accordingly, MVs produced by gram-positive and gram-negative pathogens contain toxins, virulence factors, and other molecules that promote survival in the host...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27890360/anti-tubercular-peptides-a-quest-of-future-therapeutic-weapon-to-combat-tuberculosis
#16
REVIEW
Ameer Khusro, Chirom Aarti, Paul Agastian
Tuberculosis (TB) is a symbolic menace to mankind, infecting almost one third of the world's populace and causing over a million mortalities annually. Mycobacterium tuberculosis (Mtb) is the key pathogen of TB that invades and replicates inside the host's macrophage. With the emerging dilemma of multi-drug resistant tuberculosis (MDR-TB) and extensively-drug resistant tuberculosis (XDR-TB), the exigency for developing new TB drugs is an obligation now for worldwide researchers. Among the propitious antimycobacterial agents examined in last few decades, anti-tubercular peptides have been substantiated to be persuasive with multiple advantages such as low immunogenicity, selective affinity to bacterial negatively charged cell envelopes and most importantly divergent mechanisms of action...
November 2016: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/27885799/the-c-terminal-extension-of-mycobacterium-tuberculosis-hsp16-3-regulates-its-oligomerization-subunit-exchange-dynamics-and-chaperone-function
#17
Alok Kumar Panda, Ayon Chakraborty, Sandip Kumar Nandi, Abhishek Kaushik, Ashis Biswas
Mycobacterium tuberculosis is a human pathogen that secretes a major immunodominant antigen namely Hsp16.3 throughout the course of infection. It belongs to small heat shock protein family and exhibits molecular chaperone function which is important for the growth and survival of M. tuberculosis in host cell macrophages. The importance of the N-terminal region on the structure and chaperone function of Hsp16.3 is well understood. However, the effect of the C-terminal region on these properties is far from clear...
November 25, 2016: FEBS Journal
https://www.readbyqxmd.com/read/27879023/potential-effect-of-ezetimibe-against-mycobacterium-tuberculosis-infection-in-type-ii-diabetes
#18
I-Fang Tsai, Chiu-Ping Kuo, Andrew B Lin, Ming-Nan Chien, Hsin-Tsung Ho, Tsai-Yin Wei, Chien-Liang Wu, Yen-Ta Lu
BACKGROUND AND OBJECTIVE: Tuberculosis (TB) risk might be increased in patients with diabetes by factors other than hyperglycaemia, such as dyslipidaemia. Host lipids are essential energy sources used by mycobacteria to persist in a latent TB state. A potential therapy targeting cholesterol catabolism of mycobacteria has been proposed, but the potential of cholesterol-lowering drugs as anti-TB therapy is unclear. The purpose of this study was to determine the effects of ezetimibe, a 2-azetidinone cholesterol absorption inhibitor, on intracellular mycobacteria survival and dormancy...
November 23, 2016: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/27878107/imaging-the-nadh-nad-homeostasis-for-understanding-the-metabolic-response-of-mycobacterium-to-physiologically-relevant-stresses
#19
Shabir A Bhat, Iram K Iqbal, Ashwani Kumar
The NADH:NAD(+) ratio is the primary indicator of the metabolic state of bacteria. NAD(H) homeostasis is critical for Mycobacterium tuberculosis (Mtb) survival and is thus considered an important drug target, but the spatio-temporal measurements of NAD(H) remain a challenge. Genetically encoded fluorescent biosensors of the NADH:NAD(+) ratios were recently described, paving the way for investigations of the metabolic state of pathogens during infection. Here we have adapted the genetically encoded biosensor Peredox for measurement of the metabolic state of Mtb in vitro and during infection of macrophage cells...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27867196/extracellular-adp-facilitates-monocyte-recruitment-in-bacterial-infection-via-erk-signaling
#20
Xiaoyu Zhang, Juliang Qin, Junyan Zou, Zhangsheng Lv, Binghe Tan, Jueping Shi, Yihan Zhao, Hua Ren, Mingyao Liu, Min Qian, Bing Du
As the most prominent clinical drug targets for the inhibition of platelet aggregation, P2Y12 and P2Y13 have been found to be highly expressed in both platelets and macrophages. However, the roles and function of P2Y12/13 in the regulation of macrophage-mediated innate immune responses remain unclear. Here, we demonstrate that adenosine 5'-diphosphate (ADP), the endogenous ligand of P2Y1, P2Y12 and P2Y13, was released both in E. coli-infected mice and from macrophages treated with either lipopolysaccharide (LPS) or Pam3CSK4...
November 21, 2016: Cellular & Molecular Immunology
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