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https://www.readbyqxmd.com/read/28942306/systemic-mycobacterium-kansasii-infection-in-a-domestic-shorthair-cat
#1
S-H Lee, D-M Go, S-H Woo, H-T Park, E Kim, H S Yoo, D-Y Kim
A 1-year-old, female domestic shorthair cat was presented with anorexia, depression and weight loss, accompanied by multifocal nodules affecting the face, pinnae and periarticular tissue. Routine medical treatments were ineffective. The animal's physical condition continued to deteriorate and it finally died. Post-mortem examination revealed multifocal to coalescing firm nodules with occasional ulceration affecting the ears, peri-ocular areas, nasal planum, oral cavity and laryngopharyngeal region. Tan-coloured, firm, nodular lesions were also observed in the periarticular tissue, lungs and tracheobronchial and mediastinal lymph nodes...
August 2017: Journal of Comparative Pathology
https://www.readbyqxmd.com/read/28938588/calreticulin-modulates-the-intracellular-survival-of-mycobacteria-by-regulating-er-stress-mediated-apoptosis
#2
Sung Hee Jo, Ji-Ae Choi, Yun-Ji Lim, Junghwan Lee, Soo-Na Cho, Sung-Man Oh, Dam Go, Seon-Hwa Kim, Chang-Hwa Song
Endoplasmic reticulum (ER)-stress-mediated apoptosis is a host defense mechanism against Mycobacterium tuberculosis (Mtb) infection. Calreticulin (CRT) is the major calcium-binding chaperone protein. Previous reports have suggested a close relationship between the cell-surface expression of CRT and apoptosis. In this study, the role of CRT during Mtb infection was examined. The results showed that Mtb infection induces CRT production by macrophages and that CRT levels are correlated with the degree of apoptotic cell death...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28937879/advax4-delta-inulin-combination-adjuvant-together-with-ecmx-a-fusion-construct-of-three-protective-mtb-antigens-induces-a-potent-th1-immune-response-and-protects-mice-against-mycobacterium-tuberculosis-infection
#3
Bruno de Paula Oliveira Santos, Monalisa Martins Trentini, Renato Beilner Machado, Mara Rúbia Nunes Celes, André Kipnis, Nikolai Petrovsky, Ana Paula Junqueira-Kipnis
Tuberculosis (TB) remains a main public health concern and 10.4 million new cases occurred in 2015 around the world. BCG is the only approved vaccine against TB, but has variable efficacy and new vaccines are needed. We developed two new mTB vaccine candidates based on the recombinant fusion proteins, rCMX and rECMXformulated with Advax4, a new combination adjuvant combining delta inulin, CpG oligonucleotide and murabutide. When BALB/c mice were immunized three times intramuscularly with these vaccine formulationsInjection of Advax4 alone increased the percentage of lymphatic endothelial cells and activated macrophages (F480/CD11b(+)) in the draining lymph nodes consistent with a chemotactic adjuvant effect...
September 22, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28935874/concordant-and-discordant-gene-expression-patterns-in-mouse-strains-identify-best-fit-animal-model-for-human-tuberculosis
#4
Teresa Domaszewska, Lisa Scheuermann, Karin Hahnke, Hans Mollenkopf, Anca Dorhoi, Stefan H E Kaufmann, January Weiner
Immunity in infection, inflammation and malignancy differs markedly in man and mouse. Still, we learn about human immunity in large extent from experimental mouse models. We propose a novel data integration approach which identifies concordant and discordant gene expression patterns of the immune responses in heterologous data sets. We have conducted experiments to compare human and murine transcriptional responses to Mycobacterium tuberculosis (Mtb) infection in whole blood (WB) as well as macrophages and compared them with simulated as well as publicly available data...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28935606/calcimycin-mediates-mycobacterial-killing-by-inducing-intracellular-calcium-regulated-autophagy-in-a-p2rx7-dependent-manner
#5
Shradha Mawatwal, Assirbad Behura, Abhirupa Ghosh, Saqib Kidwai, Abtar Mishra, Amar Deep, Sakshi Agarwal, Sudipto Saha, Ramandeep Singh, Rohan Dhiman
Phenotypic screening led to the identification of calcimycin as a potent inhibitor of Mycobacterium bovis BCG (M. bovis BCG) growth in vitro and in THP-1 cells. In the present study, we aim to decipher the mechanism of antimycobacterial activity of calcimycin. We noticed that treatment with calcimycin led to up-regulation of different autophagy markers like Beclin-1, autophagy-related gene (Atg) 7, Atg 3 and enhanced microtubule-associated protein 1A/1B-light chain 3-I (LC3-I) to LC3-II conversion in macrophages...
September 18, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28931237/histone-methyltransferase-set8-epigenetically-reprograms-host-immune-responses-to-assist-mycobacterial-survival
#6
Vikas Singh, Praveen Prakhar, R S Rajmani, Kasturi Mahadik, Salik Miskat Borbora, Kithiganahalli Narayanaswamy Balaji
NQO1 and TRXR1 are important host reductases implicated in the regulation of inflammation and apoptosis. Although the transcriptional machinery governing these processes have been extensively investigated, the associated epigenetic regulatory events remain unclear. Here, we report that SET8, a histone H4 lysine 20 monomethylase (H4K20me1), is highly induced during Mycobacterium tuberculosis infection that orchestrates immune evasion strategies through the induction of NQO1 and TRXR1 in vivo. SET8, along with FoxO3a, mediates an active NQO1-PGC1-α complex, which promotes the anti-inflammatory M2 macrophage phenotype, and assists TRXR1-regulated arrest of tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis...
August 15, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28925518/chemistry-of-peptidoglycan-in-mycobacterium-tuberculosis-life-style-an-off-the-wall-balance-of-synthesis-and-degradation
#7
Flavia Squeglia, Alessia Ruggiero, Rita Berisio
The cell wall envelope of mycobacteria is structurally distinct from that of both Gram-positive and Gram-negative bacteria. In Mycobacterium tuberculosis, this cell wall has unique structural features and plays a crucial role in drug resistance and macrophage survival under stress conditions. Peptidoglycan is the major constituent of this cell wall, with an important structural role, giving structural strength, and counteracting the osmotic pressure of the cytoplasm. Synthesis of this complex polymer takes place in three stages that occur at three different locations in the cell, from the cytoplasm to the external side of the cell membrane, where polymerization occurs...
September 19, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28924204/cyclipostins-and-cyclophostin-analogs-as-promising-compounds-in-the-fight-against-tuberculosis
#8
Phuong Chi Nguyen, Vincent Delorme, Anaïs Bénarouche, Benjamin P Martin, Rishi Paudel, Giri R Gnawali, Abdeldjalil Madani, Rémy Puppo, Valérie Landry, Laurent Kremer, Priscille Brodin, Christopher D Spilling, Jean-François Cavalier, Stéphane Canaan
A new class of Cyclophostin and Cyclipostins (CyC) analogs have been investigated against Mycobacterium tuberculosis H37Rv (M. tb) grown either in broth medium or inside macrophages. Our compounds displayed a diversity of action by acting either on extracellular M. tb bacterial growth only, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth with very low toxicity towards host macrophages. Among the eight potential CyCs identified, CyC 17 exhibited the best extracellular antitubercular activity (MIC50 = 500 nM)...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28922809/a-novel-ceftazidime-avibactam-rifabutin-tedizolid-and-moxifloxacin-cartm-regimen-for-pulmonary-mycobacterium-avium-disease
#9
Devyani Deshpande, Shashikant Srivastava, Jotam G Pasipanodya, Pooi S Lee, Tawanda Gumbo
Objectives: To compare the efficacy of ceftazidime/avibactam plus tedizolid-based combination regimens with the standard therapy of azithromycin, ethambutol and rifabutin for the treatment of pulmonary Mycobacterium avium complex (MAC) disease. Methods: We mimicked the human pulmonary concentration-time profiles of ceftazidime/avibactam and tedizolid in combination, ceftazidime/avibactam, rifabutin, tedizolid and moxifloxacin (CARTM), and the standard regimen and examined microbial kill in triplicate hollow-fibre system model of intracellular pulmonary MAC (HFS-MAC) units...
September 1, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28920054/controlling-extra-and-intramacrophagic-mycobacterium-abscessus-by-targeting-mycolic-acid-transport
#10
Albertus Viljoen, Jean-Louis Herrmann, Oluseye K Onajole, Jozef Stec, Alan P Kozikowski, Laurent Kremer
Mycobacterium abscessus is a rapidly growing mycobacterium (RGM) causing serious infections especially among cystic fibrosis patients. Extremely limited therapeutic options against M. abscessus and a rise in infections with this mycobacterium require novel chemotherapies and a better understanding of how the bacterium causes infection. Different from most RGM, M. abscessus can survive inside macrophages and persist for long durations in infected tissues. We recently delineated differences in the infective programs followed by smooth (S) and rough (R) variants of M...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28911035/evaluation-of-pe_pgrs33-as-a-potential-surface-target-for-humoral-responses-against-mycobacterium-tuberculosis
#11
Mariachiara Minerva, Flavio De Maio, Serena Camassa, Basem Battah, Palucci Ivana, Riccardo Manganelli, Maurizio Sanguinetti, Michela Sali, Giovanni Delogu
Mycobacterium tuberculosis (Mtb) PE_PGRS33 is a surface-exposed protein that was shown to interact with Toll-like receptor 2 on host macrophages to induce inflammatory signals and promote entry in macrophages. In this study, we investigated PE_PGRS33 as a potential target of a humoral response aimed at hampering key processes in tuberculosis pathogenesis. PE_PGRS33 protein was successfully expressed and purified under native condition in Escherichia coli. The purified protein retained its native functional and biological properties, showing the ability to elicit proinflammatory signals in murine and human macrophages...
November 30, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28910983/quantitative-proteomic-analysis-of-host-responses-triggered-by-mycobacterium-tuberculosis-infection-in-human-macrophage-cells
#12
Hua Li, Sha Wei, Yuan Fang, Min Li, Xia Li, Zhe Li, Jibin Zhang, Guofeng Zhu, Chuanyou Li, Lijun Bi, Guimin Zhang, Dianbing Wang, Xian-En Zhang
Macrophages are primary host of Mycobacterium tuberculosis (M.tb) and the central effector of in vivo innate immune responses against bacteria. Though the interaction between macrophages and mycobacteria has been widely investigated, the molecular mechanisms of M.tb pathogenesis in macrophages are still not clear. In this work, we investigated the altered protein expression profiles of macrophages after virulent H37Rv strain and avirulent H37Ra strain infection by tandem mass tag-based quantitative proteomics...
September 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28910627/dancing-with-the-stars-phenolic-glycolipids-partners-with-macrophages
#13
Micah D Dunlap, Shabaana A Khader
How Mycobacterium leprae infection causes demyelination to mediate leprosy pathogenesis has been a long-standing question. In a recent Cell paper, Madigan et al. (2017) use a zebrafish model of M. leprae infection to show that infected macrophages patrol axons to trigger mitochondrial damage and induce demyelination of nerve cells.
September 13, 2017: Cell Host & Microbe
https://www.readbyqxmd.com/read/28903728/increased-survival-and-proliferation-of-the-epidemic-strain-mycobacterium-abscessus-subsp-massiliense-crm0019-in-alveolar-epithelial-cells
#14
Giovanni Monteiro Ribeiro, Cristianne Kayoko Matsumoto, Fernando Real, Daniela Teixeira, Rafael Silva Duarte, Renato Arruda Mortara, Sylvia Cardoso Leão, Cristiane de Souza Carvalho-Wodarz
BACKGROUND: Outbreaks of infections caused by rapidly growing mycobacteria have been reported worldwide generally associated with medical procedures. Mycobacterium abscessus subsp. massiliense CRM0019 was obtained during an epidemic of postsurgical infections and was characterized by increased persistence in vivo. To better understand the successful survival strategies of this microorganism, we evaluated its infectivity and proliferation in macrophages (RAW and BMDM) and alveolar epithelial cells (A549)...
September 13, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28893784/the-dual-mechanism-of-action-of-5-nitro-1-10-phenanthroline-against-mycobacterium-tuberculosis
#15
Saqib Kidwai, Chan-Yong Park, Shradha Mawatwal, Prabhakar Tiwari, Myung Geun Jung, Tannu Priya Gosain, Pradeep Kumar, David Alland, Sandeep Kumar, Avinash Bajaj, Yun-Kyung Hwang, Chang Sik Song, Rohan Dhiman, Ill Young Lee, Ramandeep Singh
New chemotherapeutics agents with novel mechanism of action are urgently required to combat the challenge imposed by the emergence of drug resistant mycobacteria. In this study, a phenotypic whole cell screen identified 5-nitro-1,10-phenanthroline (5NP) as a lead compound. 5NP resistant isolates harbored mutations mapped to fbiB and were also resistant to bicyclic nitroimidazole, PA-824. Mechanistic studies confirmed that 5NP is activated in F420 dependent manner resulting in formation of 1,10-phenanthroline and 1,10-phenanthrolin-5-amine as major metabolites in bacteria...
September 11, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28893617/therapeutic-potential-of-carbohydrates-as-regulators-of-macrophage-activation
#16
REVIEW
Mimmi L E Lundahl, Eoin M Scanlan, Ed C Lavelle
It is well established for a broad range of disease states, including cancer and Mycobacterium tuberculosis infection, that pathogenesis is bolstered by polarisation of macrophages towards an anti-inflammatory phenotype, known as M2. As these innate immune cells are relatively long-lived, their re-polarisation to pro-inflammatory, phagocytic and bactericidal "classically activated" M1 macrophages is an attractive therapeutic approach. On the other hand, there are scenarios where the resolving inflammation, wound healing and tissue remodelling properties of M2 macrophages are beneficial - for example the successful introduction of biomedical implants...
September 8, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28892415/susceptibility-of-m-tuberculosis-infected-host-cells-to-phospho-mlkl-driven-necroptosis-is-dependent-on-cell-type-and-presence-of-tnf%C3%AE
#17
Rachel E Butler, Nitya Krishnan, Waldo Garcia-Jimenez, Robert Francis, Abbe Martyn, Tom Mendum, Shaza Felemban, Nicolas Locker, Javier Salguero-Bodes, Brian Robertson, Graham R Stewart
An important feature of Mycobacterium tuberculosis pathogenesis is the ability to control cell death in infected host cells, including inhibition of apoptosis and stimulation of necrosis. Recently an alternative form of programmed cell death, necroptosis, has been described where necrotic cell death is induced by apoptotic stimuli under conditions where apoptotic execution is inhibited. We show for the first time that M. tuberculosis and TNFα synergise to induce necroptosis in murine fibroblasts via RIPK1-dependent mechanisms and characterized by phosphorylation of Ser345 of the MLKL necroptosis death effector...
September 11, 2017: Virulence
https://www.readbyqxmd.com/read/28890547/innate-immunity-in-tuberculosis-host-defense-vs-pathogen-evasion
#18
REVIEW
Cui Hua Liu, Haiying Liu, Baoxue Ge
The major innate immune cell types involved in tuberculosis (TB) infection are macrophages, dendritic cells (DCs), neutrophils and natural killer (NK) cells. These immune cells recognize the TB-causing pathogen Mycobacterium tuberculosis (Mtb) through various pattern recognition receptors (PRRs), including but not limited to Toll-like receptors (TLRs), Nod-like receptors (NLRs) and C-type lectin receptors (CLRs). Upon infection by Mtb, the host orchestrates multiple signaling cascades via the PRRs to launch a variety of innate immune defense functions such as phagocytosis, autophagy, apoptosis and inflammasome activation...
September 11, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28882483/profiling-of-in-vitro-activities-of-urea-based-inhibitors-against-cysteine-synthases-from-mycobacterium-tuberculosis
#19
Katharina Brunner, Eva Maria Steiner, Rudraraju Srilakshmi Reshma, Dharmarajan Sriram, Robert Schnell, Gunter Schneider
CysK1 and CysK2 are two members of the cysteine/S-sulfocysteine synthase family in Mycobacterium tuberculosis, responsible for the de novo biosynthesis of l-cysteine, which is subsequently used as a building block for mycothiol. This metabolite is the first line defense of this pathogen against reactive oxygen and nitrogen species released by host macrophages after phagocytosis. In a previous medicinal chemistry campaign we had developed urea-based inhibitors of the cysteine synthase CysM with bactericidal activity against dormant M...
August 19, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28880895/lag-3-potentiates-the-survival-of-mycobacterium-tuberculosis-in-host-phagocytes-by-modulating-mitochondrial-signaling-in-an-in-vitro-granuloma-model
#20
Bonnie L Phillips, Uma S Gautam, Allison N Bucsan, Taylor W Foreman, Nadia A Golden, Tianhua Niu, Deepak Kaushal, Smriti Mehra
CD4+ T-cell mediated Th1 immune responses are critical for immunity to TB. The immunomodulatory protein, lymphocyte activation gene-3 (LAG-3) decreases Th1-type immune responses in T-cells. LAG-3 expression is significantly induced in the lungs of macaques with active TB and correlates with increased bacterial burden. Overproduction of LAG-3 can greatly diminish responses and could lead to uncontrolled Mtb replication. To assess the effect of LAG-3 on the progression of Mtb infection, we developed a co-culture system wherein blood-derived macrophages are infected with Mtb and supplemented with macaque blood or lung derived CD4+ T-cells...
2017: PloS One
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