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https://www.readbyqxmd.com/read/27908271/host-directed-therapeutics-against-mycobacterial-infections
#1
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/27906132/the-distinct-fate-of-smooth-and-rough-mycobacterium-abscessus-variants-inside-macrophages
#2
Anne-Laure Roux, Albertus Viljoen, Aïcha Bah, Roxane Simeone, Audrey Bernut, Laura Laencina, Therese Deramaudt, Martin Rottman, Jean-Louis Gaillard, Laleh Majlessi, Roland Brosch, Fabienne Girard-Misguich, Isabelle Vergne, Chantal de Chastellier, Laurent Kremer, Jean-Louis Herrmann
Mycobacterium abscessus is a pathogenic, rapidly growing mycobacterium responsible for pulmonary and cutaneous infections in immunocompetent patients and in patients with Mendelian disorders, such as cystic fibrosis (CF). Mycobacterium abscessus is known to transition from a smooth (S) morphotype with cell surface-associated glycopeptidolipids (GPL) to a rough (R) morphotype lacking GPL. Herein, we show that M. abscessus S and R variants are able to grow inside macrophages and are present in morphologically distinct phagosomes...
November 2016: Open Biology
https://www.readbyqxmd.com/read/27905994/the-role-of-il-10-in-mycobacterium-avium-subsp-paratuberculosis-infection
#3
REVIEW
Tariq Hussain, Syed Zahid Ali Shah, Deming Zhao, Srinand Sreevatsan, Xiangmei Zhou
Mycobacterium avium subsp. paratuberculosis (MAP) is an intracellular pathogen and is the causative agent of Johne's disease of domestic and wild ruminants. Johne's disease is characterized by chronic granulomatous enteritis leading to substantial economic losses to the livestock sector across the world. MAP persistently survives in phagocytic cells, most commonly in macrophages by disrupting its early antibacterial activity. MAP triggers several signaling pathways after attachment to pathogen recognition receptors (PRRs) of phagocytic cells...
December 1, 2016: Cell Communication and Signaling: CCS
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
#4
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
#5
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
#6
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/27893778/mycobacterium-ulcerans-mouse-model-refinement-for-pre-clinical-profiling-of-vaccine-candidates
#7
Angèle Bénard, Claudia Sala, Gerd Pluschke
Buruli Ulcer is a neglected tropical disease leading to extensive disabilities and morbidity in West Africa. In this paper we sought to characterize various strains of Mycobacterium ulcerans (M.ulcerans) with different origins and laboratory passage records while refining a mouse model for Buruli ulcer. We described, compared and followed the kinetics of the histo-pathological outcome of infection of a collection of strains at various anatomical sites of infection in order to find a suitable model for further immunization studies...
2016: PloS One
https://www.readbyqxmd.com/read/27892584/a-short-history-of-phototherapy-vitamin-d-and-skin-disease
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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/27867377/over-expression-of-the-mycobacterial-trehalose-phosphate-phosphatase-otsb2-results-in-a-defect-in-macrophage-phagocytosis-associated-with-increased-mycobacterial-macrophage-adhesion
#14
Hao Li, Mei Wu, Yan Shi, Babak Javid
Trehalose-6-phosphate phosphatase (OtsB2) is involved in the OtsAB trehalose synthesis pathway to produce free trehalose and is strictly essential for mycobacterial growth. We wished to determine the effects of OtsB2 expression on mycobacterial phenotypes such as growth, phagocytosis and survival in macrophages. Mycobacterium bovis-bacillus calmette-guerin (BCG) over-expressing OtsB2 were able to better survive in stationary phase. Over-expression of OtsB2 led to a decrease in phagocytosis but not survival in THP-1 macrophage-like cells, and this was not due to a decrease in general macrophage phagocytic activity...
2016: Frontiers in Microbiology
https://www.readbyqxmd.com/read/27866220/molecular-basis-of-mycobacterial-survival-in-macrophages
#15
REVIEW
Jane Atesoh Awuh, Trude Helen Flo
Macrophages play an essential role in the immune system by ingesting and degrading invading pathogens, initiating an inflammatory response and instructing adaptive immune cells, and resolving inflammation to restore homeostasis. More interesting is the fact that some bacteria have evolved to use macrophages as a natural habitat and tools of spread in the host, e.g., Mycobacterium tuberculosis (Mtb) and some non-tuberculous mycobacteria (NTM). Mtb is considered one of humanity's most successful pathogens and is the causal agent of tuberculosis, while NTMs cause opportunistic infections all of which are of significant public health concern...
November 19, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27865402/some-proteins-of-m-%C3%A2-tuberculosis-that-localise-to-the-nucleus-of-thp-1-derived-macrophages
#16
Atul Kumar Agrawal, Rajeev Ranjan, Sharat Chandra, Tofan Kumar Rout, Amit Misra, Thota Jagadeshwar Reddy
Host-pathogen dialectics in tuberculosis (TB) via DNA-protein interactions are emerging. We investigated whether proteins produced by Mycobacterium tuberculosis (Mtb) could translocate to the host nucleus. Using lysates of nuclei purified from Mtb-infected THP-1-derived macrophages, we identified at least 15 proteins of Mtb-origin by electrophoretic and chromatographic separation and mass spectrometry. Western blotting confirmed time-dependent accumulation of Mtb EF-Tu, GroEL, GroES and MtrA in the host nucleus...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27865392/mycobacterium-indicus-pranii-mip-mediated-host-protective-intracellular-mechanisms-against-tuberculosis-infection-involvement-of-tlr-4-mediated-signaling
#17
Shibali Das, Bidisha Paul Chowdhury, Avranil Goswami, Shabina Parveen, Junaid Jawed, Nishith Pal, Subrata Majumdar
Mycobacterium tuberculosis infection inflicts the disease Tuberculosis (TB), which is fatal if left untreated. During M. tuberculosis infection, the pathogen modulates TLR-4 receptor down-stream signaling, indicating the possible involvement of TLR-4 in the regulation of the host immune response. Mycobacterium indicus pranii (MIP) possesses immuno-modulatory properties which induces the pro-inflammatory responses via induction of TLR-4-mediated signaling. Here, we observed the immunomodulatory properties of MIP against tuberculosis infection...
December 2016: Tuberculosis
https://www.readbyqxmd.com/read/27858493/sp110b-controls-host-immunity-and-susceptibility-to-tuberculosis
#18
Jia-Shiun Leu, Mei-Ling Chen, So-Yi Chang, Sung-Liang Yu, Chia-Wei Lin, Hsuan Wang, Wan-Chen Chen, Chin-Hao Chang, Jann-Yuan Wang, Li-Na Lee, Chong-Jen Yu, Igor Kramnik, Bo-Shiun Yan, Pan-Chyr Yang
RATIONALE: How host genetic factors affect Mycobacterium tuberculosis (Mtb) infection outcomes remains largely unknown. SP110b, an interferon (IFN)-induced nuclear protein, is the nearest human homolog to the mouse Ipr1 protein that has been shown to control host innate immunity to Mtb infection. However, the function(s) of SP110b remain unclear. OBJECTIVES: To elucidate the role of SP110b in controlling the host immunity and susceptibility to tuberculosis (TB) as well as to identify the fundamental immunological and molecular mechanisms affected by SP110b...
November 18, 2016: American Journal of Respiratory and Critical Care Medicine
https://www.readbyqxmd.com/read/27856731/airway-delivery-of-interferon-%C3%AE-overexpressing-macrophages-confers-resistance-to-mycobacterium-avium-infection-in-scid-mice
#19
Rajamouli Pasula, Bradley E Britigan, Banurekha Kesavalu, Maher Y Abdalla, William J Martin
Mycobacterium avium (M. avium) causes significant pulmonary infection, especially in immunocompromised hosts. Alveolar macrophages (AMs) represent the first line of host defense against infection in the lung. Interferon gamma (IFN-γ) activation of AMs enhances in vitro killing of pathogens such as M. avium We hypothesized that airway delivery of AMs into the lungs of immunodeficient mice infected with M. avium will inhibit M. avium growth in the lung and that this macrophage function is in part IFN-γ dependent...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27854511/a-negative-feedback-loop-between-autophagy-and-immune-responses-in-mycobacterium-leprae-infection
#20
Yuelong Ma, Li Zhang, Jie Lu, Tiejun Shui, Jia Chen, Jun Yang, Joanna Yuan, Yeqiang Liu, Degang Yang
The obligate intracellular bacterium Mycobacterium leprae is the causative agent of leprosy and primarily infects macrophages, leading to irreversible nerve damage and deformities. So far, the underlying reasons allowing M. leprae to persist and propagate in macrophages, despite the presence of cellular immunity, are still a mystery. Here, we investigated the role of autophagy, a cellular process that degrades cytosolic materials and intracellular pathogens, in M. leprae infection. We found that live M. leprae infection of macrophages resulted in significantly elevated autophagy level...
November 17, 2016: DNA and Cell Biology
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