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https://read.qxmd.com/read/30876870/host-directed-therapies-to-combat-tuberculosis-and-associated-non-communicable-diseases
#1
REVIEW
Piyush Baindara
Mycobacterium tuberculosis (Mtb) has coevolved with a human host to evade and exploit the immune system in multiple ways. Mtb is an enormously successful human pathogen that can remain undetected in hosts for decades without causing clinical disease. While tuberculosis (TB) represents a perfect prototype of host-pathogen interaction, it remains a major challenge to develop new therapies to combat mycobacterial infections. Additionally, recent studies emphasize on comorbidity of TB with different non-communicable diseases (NCDs), highlighting the impact of demographic and lifestyle changes on the global burden of TB...
March 12, 2019: Microbial Pathogenesis
https://read.qxmd.com/read/30867005/impact-of-obesity-on-breast-cancer-recurrence-and-minimal-residual-disease
#2
Brett L Ecker, Jun Y Lee, Christopher J Sterner, Aaron C Solomon, Dhruv K Pant, Fei Shen, Javier Peraza, Lauren Vaught, Samyukta Mahendra, George K Belka, Tien-Chi Pan, Kathryn H Schmitz, Lewis A Chodosh
BACKGROUND: Obesity is associated with an increased risk of breast cancer recurrence and cancer death. Recurrent cancers arise from the pool of residual tumor cells, or minimal residual disease (MRD), that survives primary treatment and persists in the host. Whether the association of obesity with recurrence risk is causal is unknown, and the impact of obesity on MRD and breast cancer recurrence has not been reported in humans or in animal models. METHODS: Doxycycline-inducible primary mammary tumors were generated in intact MMTV-rtTA;TetO-HER2/neu (MTB/TAN) mice or orthotopic recipients fed a high-fat diet (HFD; 60% kcal from fat) or a control low-fat diet (LFD; 10% kcal from fat)...
March 13, 2019: Breast Cancer Research: BCR
https://read.qxmd.com/read/30865638/pasakbumin-a-controls-the-growth-of-mycobacterium-tuberculosis-by-enhancing-the-autophagy-and-production-of-antibacterial-mediators-in-mouse-macrophages
#3
Hyo-Ji Lee, Hyun-Jeong Ko, Seung Hyun Kim, Yu-Jin Jung
Tuberculosis (TB) is a chronic infectious disease caused by Mycobacterium tuberculosis (Mtb) and remains a major health problem worldwide. Thus, identification of new and more effective drugs to treat emerging multidrug-resistant TB (MDR-TB) and to reduce the side effects of anti-TB drugs, such as liver toxicity and other detrimental changes, is urgently needed. In this study, to develop a novel candidate drug for effective TB treatment with few side effects in the host, we selected pasakbumin A isolated from Eurycoma longifolia (E...
2019: PloS One
https://read.qxmd.com/read/30862753/the-polar-organizing-protein-popz-is-fundamental-for-proper-cell-division-and-segregation-of-cellular-content-in-magnetospirillum-gryphiswaldense
#4
Daniel Pfeiffer, Mauricio Toro-Nahuelpan, Marc Bramkamp, Jürgen M Plitzko, Dirk Schüler
Magnetotactic bacteria (MTB) are of special scientific interest due to the formation of magnetosomes, intracellular membrane-enveloped magnetite crystals arranged into a linear chain by a dedicated cytoskeleton. Magnetotaxis relies on the formation and proper inheritance of these unique magnetic organelles, both of which need to be coordinated with the segregation of other cellular content such as chromosomes or motility and chemotaxis related structures. Thus, elaborated mechanisms are required in MTB to coordinate and maintain a high level of spatial and temporal subcellular organization during cytokinesis...
March 12, 2019: MBio
https://read.qxmd.com/read/30858471/characterisation-of-genes-differentially-expressed-in-macrophages-by-virulent-and-attenuated-mycobacterium-tuberculosis-through-rna-seq-analysis
#5
Junghwan Lee, Sung-Gwon Lee, Kee K Kim, Yun-Ji Lim, Ji-Ae Choi, Soo-Na Cho, Chungoo Park, Chang-Hwa Song
Tuberculosis (TB) remains a global healthcare issue. Understanding the host-pathogen interactions in TB is vital to develop strategies and therapeutic tools for the control of Mycobacterium tuberculosis (Mtb). In this study, transcriptome analyses of macrophages infected with either the virulent Mtb strain H37Rv (Rv) or the avirulent Mtb strain H37Ra (Ra) were carried out and 750 differentially expressed genes (DEGs) were identified. As expected, the DEGs were mainly involved in the induction of innate immune responses against mycobacterial infections...
March 11, 2019: Scientific Reports
https://read.qxmd.com/read/30856410/the-mycobacterium-tuberculosis-glycoprotein-rv1016c-protein-inhibits-dendritic-cell-maturation-and-impairs-th1-th17-responses-during-mycobacteria-infection
#6
Haibo Su, Baozhou Peng, Zhen Zhang, Zijian Liu, Zhi Zhang
The myobacterial factors and the associated mechanism by which Mycobacterium tuberculosis (Mtb) evades the host immune surveillance system remain widely unexplored. Here, we found that overexpressing Rv1016c, a mannosylated protein of M. tuberculosis in BCG (rBCG-Rv1016c) led to increased virulence of the recombined BCG in the severe-combined immunodeficient (SCID) mice model and to a loss of protective efficacy in a zebrafish-M. marinum model, compared to wild type BCG. Further investigations on the effects of rBCG-Rv1016c on the host innate immunity revealed that rBCG-Rv1016c decreased the production of cytokines IL-2, IL-12p70, TGF-β, IL-6 as well as of the co-stimulatory molecules CD80, CD86, MHC-I and MHC-II by the infected DCs...
March 8, 2019: Molecular Immunology
https://read.qxmd.com/read/30841927/engineered-magnetosomes-fused-to-functional-molecule-protein-a-provide-a-highly-effective-alternative-to-commercial-immunomagnetic-beads
#7
Junjie Xu, Lingzi Liu, Jinxin He, Shijiao Ma, Shuli Li, Zhanhui Wang, Ting Xu, Wei Jiang, Ying Wen, Ying Li, Jiesheng Tian, Feng Li
BACKGROUND: Magnetosomes (also called bacterial magnetic nanoparticles; BMPs) are biomembrane-coated nanoparticles synthesized by magnetotactic bacteria (MTB). Engineered BMPs fused to protein A (termed ∆F-BMP-FA) bind antibodies (Abs) automatically, and thus provide a series of potential advantages. However, no report so far has systematically evaluated functional applicability of genetically engineered BMPs. RESULTS: We evaluated properties of ∆F-BMP-FA, and developed/optimized culture methods for host strain Magnetospirillum gryphiswaldense ΔF-FA, ∆F-BMP-FA extraction conditions, conditions for Ab conjugation to ∆F-BMP-FA surface, and procedures for antigen detection using ∆F-BMP-FA/Ab complexes (termed BMP-A-Ab)...
March 6, 2019: Journal of Nanobiotechnology
https://read.qxmd.com/read/30822547/latent-tb-infection-ltbi-mycobacterium-tuberculosis-pathogenesis-and-the-dynamics-of-the-granuloma-battleground
#8
Martin Rao, Giuseppe Ippolito, Sayoki Mfinanga, Francine Ntoumi, Dorothy Yeboah-Manu, Cristina Vilaplana, Alimuddin Zumla, Markus Maeurer
Latent tuberculosis infection (LTBI) is established in over 90% of persons infected with Mycobacterium tuberculosis (Mtb), from among whom new active TB cases will arise. As such, understanding the dynamics of host responses in LTBI granulomas in the lung is essential to designing effective post-exposure therapies that inhibit progression to TB. Information arising from cancer studies and other modalities - where local chronic inflammation leads to immunopathology - can help provide insights into the biological pathways at play in LTBI granulomas...
February 26, 2019: International Journal of Infectious Diseases: IJID
https://read.qxmd.com/read/30814998/evidence-for-highly-variable-region-specific-patterns-of-t-cell-epitope-mutations-accumulating-in-mycobacterium-tuberculosis-strains
#9
Arunachalam Ramaiah, Soumya Nayak, Srabanti Rakshit, Abigail L Manson, Thomas Abeel, Sivakumar Shanmugam, Pravat Nalini Sahoo, Anto Jesuraj Uday Kumar John, Jagadish Chandrabose Sundaramurthi, Sujatha Narayanan, George D'Souza, Paul von Hoegen, Tom H M Ottenhoff, Soumya Swaminathan, Ashlee M Earl, Annapurna Vyakarnam
Vaccines that confer protection through induction of adaptive T-cell immunity rely on understanding T-cell epitope (TCE) evolution induced by immune escape. This is poorly understood in tuberculosis (TB), an ancient, chronic disease, where CD4 T-cell immunity is of recognized importance. We probed 905 functionally validated, curated human CD4 T cell epitopes in 79 Mycobacterium tuberculosis (Mtb) whole genomes from India. This screen resulted in identifying 64 mutated epitopes in these strains initially using a computational pipeline and subsequently verified by single nucleotide polymorphism (SNP) analysis...
2019: Frontiers in Immunology
https://read.qxmd.com/read/30787033/a-major-role-for-ferroptosis-in-mycobacterium-tuberculosis-induced-cell-death-and-tissue-necrosis
#10
Eduardo P Amaral, Diego L Costa, Sivaranjani Namasivayam, Nicolas Riteau, Olena Kamenyeva, Lara Mittereder, Katrin D Mayer-Barber, Bruno B Andrade, Alan Sher
Necrotic cell death during Mycobacterium tuberculosis (Mtb) infection is considered host detrimental since it facilitates mycobacterial spread. Ferroptosis is a type of regulated necrosis induced by accumulation of free iron and toxic lipid peroxides. We observed that Mtb-induced macrophage necrosis is associated with reduced levels of glutathione and glutathione peroxidase-4 (Gpx4), along with increased free iron, mitochondrial superoxide, and lipid peroxidation, all of which are important hallmarks of ferroptosis...
February 20, 2019: Journal of Experimental Medicine
https://read.qxmd.com/read/30783183/intestinal-dysbiosis-compromises-alveolar-macrophage-immunity-to-mycobacterium-tuberculosis
#11
Nargis Khan, Laura Mendonca, Achal Dhariwal, Ghislaine Fontes, Dick Menzies, Jianguo Xia, Maziar Divangahi, Irah L King
Current treatments for tuberculosis (TB) are effective in controlling Mycobacterium tuberculosis (Mtb) growth, yet have significant side effects and do not prevent reinfection. Therefore, it is critical to understand why our host defense system is unable to generate permanent immunity to Mtb despite prolonged anti-tuberculosis therapy (ATT). Here, we demonstrate that treatment of mice with the most widely used anti-TB drugs, rifampicin (RIF) or isoniazid (INH) and pyrazinamide (PYZ), significantly altered the composition of the gut microbiota...
February 19, 2019: Mucosal Immunology
https://read.qxmd.com/read/30754665/investigating-the-role-of-everolimus-in-mtor-inhibition-and-autophagy-promotion-as-a-potential-host-directed-therapeutic-target-in-mycobacterium-tuberculosis-infection
#12
REVIEW
Stephen Cerni, Dylan Shafer, Kimberly To, Vishwanath Venketaraman
Tuberculosis (TB) is a serious infectious disease caused by the pathogen Mycobacterium tuberculosis ( Mtb ). The current therapy consists of a combination of antibiotics over the course of four months. Current treatment protocols run into problems due to the growing antibiotic resistance of Mtb and poor compliance to the multi-drug-resistant TB treatment protocol. New treatments are being investigated that target host intracellular processes that could be effective in fighting Mtb infections. Autophagy is an intracellular process that is involved in eliminating cellular debris, as well as intracellular pathogens...
February 11, 2019: Journal of Clinical Medicine
https://read.qxmd.com/read/30743161/identification-of-glucosyl-3-phosphoglycerate-phosphatase-as-a-novel-drug-target-against-resistant-strain-of-mycobacterium-tuberculosis-xdr1219-by-using-comparative-metabolic-pathway-approach
#13
Reaz Uddin, Noor-Ul-Ain Zahra, Syed Sikander Azam
Tuberculosis (TB) is a major global health challenge. It has been afflicting human for thousands of years and is still severely affecting a huge population. The etiological agent of the disease is Mycobacterium tuberculosis (MTB) that survives in the human host in latent, dormant, and non-replicative state by evading the immune system. It is one of the leading causes of infection related death worldwide. The situation is exacerbated by the massive increase in the resistant strains such as multi-drug resistant TB (MDR-TB) and extensive drug-resistant TB (XDR-TB)...
January 24, 2019: Computational Biology and Chemistry
https://read.qxmd.com/read/30740456/the-extracellular-matrix-of-mycobacterial-biofilms-could-we-shorten-the-treatment-of-mycobacterial-infections
#14
REVIEW
Poushali Chakraborty, Ashwani Kumar
A number of non-tuberculous mycobacterium species are opportunistic pathogens and ubiquitously form biofilms. These infections are often recalcitrant to treatment and require therapy with multiple drugs for long duration. The biofilm resident bacteria also display phenotypic drug tolerance and thus it has been hypothesized that the drug unresponsiveness in vivo could be due to formation of biofilms inside the host. We have discussed the biofilms of several pathogenic non-tuberculous mycobacterium (NTM) species in context to the in vivo pathologies...
January 18, 2019: Microbial Cell
https://read.qxmd.com/read/30737374/corticosteroids-inhibit-mycobacterium-tuberculosis-induced-necrotic-host-cell-death-by-abrogating-mitochondrial-membrane-permeability-transition
#15
Jessica Gräb, Isabelle Suárez, Edeltraud van Gumpel, Sandra Winter, Fynn Schreiber, Anna Esser, Christoph Hölscher, Melanie Fritsch, Marc Herb, Michael Schramm, Laurens Wachsmuth, Christian Pallasch, Manolis Pasparakis, Hamid Kashkar, Jan Rybniker
Corticosteroids are host-directed drugs with proven beneficial effect on survival of tuberculosis (TB) patients, but their precise mechanisms of action in this disease remain largely unknown. Here we show that corticosteroids such as dexamethasone inhibit necrotic cell death of cells infected with Mycobacterium tuberculosis (Mtb) by facilitating mitogen-activated protein kinase phosphatase 1 (MKP-1)-dependent dephosphorylation of p38 MAPK. Characterization of infected mixed lineage kinase domain-like (MLKL) and tumor necrosis factor receptor 1 (TNFR1) knockout cells show that the underlying mechanism is independent from TNFα-signaling and necroptosis...
February 8, 2019: Nature Communications
https://read.qxmd.com/read/30717477/different-signaling-pathways-define-different-interferon-stimulated-gene-expression-during-mycobacteria-infection-in-macrophages
#16
Xinying Zhou, Jiahui Yang, Zelin Zhang, Lijie Zhang, Bo Zhu, Linmiao Lie, Yubin Huang, Rui Ma, Chaoying Zhou, Shengfeng Hu, Qian Wen, Li Ma
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) represents one of the greatest threats to human health., Interferons (IFNs) in combination with the first-line of anti-TB drugs have been used for treating TB for decades in the clinic, but how Mtb infection regulates interferon-stimulated genes (ISGs) in human macrophages (Mϕs) remains unknown. In this study, we investigated the expression-signature and associated innate signaling mechanisms of ISGs in Mtb-infected human monocyte-derived Mϕs (hMDMs) and THP-1-derived Mϕs (THP-1-Mϕs)...
February 3, 2019: International Journal of Molecular Sciences
https://read.qxmd.com/read/30716121/potassium-response-and-homeostasis-in-mycobacterium-tuberculosis-modulates-environmental-adaptation-and-is-important-for-host-colonization
#17
Nathan J MacGilvary, Yuzo L Kevorkian, Shumin Tan
Successful host colonization by bacteria requires sensing and response to the local ionic milieu, and coordination of responses with the maintenance of ionic homeostasis in the face of changing conditions. We previously discovered that Mycobacterium tuberculosis (Mtb) responds synergistically to chloride (Cl-) and pH, as cues to the immune status of its host. This raised the intriguing concept of abundant ions as important environmental signals, and we have now uncovered potassium (K+) as an ion that can significantly impact colonization by Mtb...
February 4, 2019: PLoS Pathogens
https://read.qxmd.com/read/30711546/mycobacterium-tuberculosis-ag85b-hfc%C3%AE-1-recombinant-fusion-protein-as-a-selective-receptor-dependent-delivery-system-for-antigen-presentation
#18
Mohsen Karbalaei Zadeh Babaki, Mahboubeh Taghiabadi, Saman Soleimanpour, Masoud Saleh Moghadam, Arman Mosavat, Abbas Ali Amini, Mohammad Ali Mohammadi, Seyed Abdolrahim Rezaee
Introducing an effective vaccine for tuberculosis (TB) is an urgent need. Mycobacterium tuberculosis (Mtb) Ag85 complex is suggested for making protective immunodominant antigens for design and development of novel TB vaccine. In the present study, a pDR2EF1-Fcγ1 vector has been used to make Ag85B:hFcγ1 recombinant fusion protein. Briefly, specific XbaI and NotI site incorporated primers were used to amplify Mtb-fbpB gene by PCR, TA-cloned and amplified in E.coli DH5α. The resulting vector then subcloned into the pDR2EF1...
January 31, 2019: Microbial Pathogenesis
https://read.qxmd.com/read/30711161/mycobacterium-tuberculosis-with-different-virulence-reside-within-intact-phagosomes-and-inhibit-phagolysosomal-biogenesis-in-alveolar-macrophages-of-patients-with-pulmonary-tuberculosis
#19
Elena Ufimtseva, Natalya Eremeeva, Sergey Bayborodin, Tatiana Umpeleva, Diana Vakhrusheva, Sergey Skornyakov
Tuberculosis (TB) is a dangerous airborne disease caused by Mycobacterium tuberculosis (Mtb) and characterized by a tight interplay between pathogen and host cells, mainly alveolar macrophages. Studies of the mechanisms of Mtb survival within human cells during TB disease are extremely important for the development of new strategies and drugs for TB treatment. We have used the ex vivo cultures of alveolar macrophages and histological sections obtained from the resected lungs of patients with pulmonary TB to establish the unique features of Mtb lifestyle in host cells...
January 2019: Tuberculosis
https://read.qxmd.com/read/30711151/valproic-acid-promotes-a-decrease-in-mycobacterial-survival-by-enhancing-nitric-oxide-production-in-macrophages-stimulated-with-ifn-%C3%AE
#20
Erik Nieto-Patlán, Jeanet Serafín-López, Isabel Wong-Baeza, Sonia M Pérez-Tapia, Laura Cobos-Marín, Sergio Estrada-Parra, Iris Estrada-García, Alma D Chávez-Blanco, Rommel Chacón-Salinas
Tuberculosis is one of the leading causes of mortality worldwide, it is caused by Mycobacterium tuberculosis (Mtb), a bacteria that employs several strategies to evade the host immune response. For instance, Mtb interferes with the overexpression of class II transactivator (CIITA) in macrophages exposed to IFN-γ by inhibiting histone acetylation at its promoter, which can be reverted by the histone deacetylase inhibitor (HDACi) sodium butyrate. In this work, we evaluated whether a different HDACi, valproic acid (VPA), could revert the inhibition of gene expression induced by Mtb...
January 2019: Tuberculosis
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