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https://www.readbyqxmd.com/read/28713776/modulation-of-trehalose-dimycolate-and-immune-system-by-rv0774c-protein-enhanced-the-intracellular-survival-of-mycobacterium-smegmatis-in-human-macrophages-cell-line
#1
Arbind Kumar, Varinder Saini, Anjani Kumar, Jasbinder Kaur, Jagdeep Kaur
Mycobacterium tuberculosis Rv0774c protein was reported previously to express under stress conditions. Therefore, Rv0774c gene was cloned and expressed in Mycobacterium smegmatis, a surrogate host, to determine its role in bacterial persistence and immune modulation in natural environment. The bacterial colonies expressing Rv0774c (Ms_rv0774c) were larger, smoother, more moist, and flatter than the control ones (Ms_ve). Enhanced survival of Ms_rv0774c after treatment with streptomycin was observed when compared with control...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28712709/synthesis-and-biological-evaluation-of-novel-1-2-3-triazole-derivatives-as-anti-tubercular-agents
#2
Abdul Aziz Ali, Dhrubajyoti Gogoi, Amrita K Chaliha, Alak K Buragohain, Priyanka Trivedi, Prakash J Saikia, Praveen S Gehlot, Arvind Kumar, Vinita Chaturvedi, Diganta Sarma
A library of seventeen novel 1,2,3-triazole derivatives were efficiently synthesized in excellent yields by the popular 'click chemistry' approach and evaluated in vitro for their anti-tubercular activity against Mycobacterium tuberculosis H37Ra (ATCC 25177 strain). Among the series, six compounds exhibited significant activity with minimum inhibitory concentration (MIC) values ranging from 3.12 to 0.78μg/mL and along with no significant cytotoxicity against MBMDMQs (mouse bone marrow derived macrophages)...
July 5, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28711989/striking-the-right-immunological-balance-prevents-progression-of-tuberculosis
#3
REVIEW
Shachi Pranjal Vyas, Ritobrata Goswami
INTRODUCTION: Tuberculosis (TB) caused by infection with Mycobacterium tuberculosis (Mtb) is a major burden for human health worldwide. Current standard treatments for TB require prolonged administration of antimycobacterial drugs leading to exaggerated inflammation and tissue damage. This can result in the reactivation of latent TB culminating in TB progression. Thus, there is an unmet need to develop therapies that would shorten the duration of anti-TB treatment and to induce optimal protective immune responses to control the spread of mycobacterial infection with minimal lung pathology...
July 15, 2017: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/28710351/combination-therapy-for-tuberculosis-treatment-pulmonary-administration-of-ethionamide-and-booster-co-loaded-nanoparticles
#4
Joana Costa-Gouveia, Elisabetta Pancani, Samuel Jouny, Arnaud Machelart, Vincent Delorme, Giuseppina Salzano, Raffaella Iantomasi, Catherine Piveteau, Christophe J Queval, Ok-Ryul Song, Marion Flipo, Benoit Deprez, Jean-Paul Saint-André, José Hureaux, Laleh Majlessi, Nicolas Willand, Alain Baulard, Priscille Brodin, Ruxandra Gref
Tuberculosis (TB) is a leading infectious cause of death worldwide. The use of ethionamide (ETH), a main second line anti-TB drug, is hampered by its severe side effects. Recently discovered "booster" molecules strongly increase the ETH efficacy, opening new perspectives to improve the current clinical outcome of drug-resistant TB. To investigate the simultaneous delivery of ETH and its booster BDM41906 in the lungs, we co-encapsulated these compounds in biodegradable polymeric nanoparticles (NPs), overcoming the bottlenecks inherent to the strong tendency of ETH to crystallize and the limited water solubility of this Booster...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28710015/bactericidal-impact-of-ag-zno-and-mixed-agzno-colloidal-nanoparticles-on-h37rv-mycobacterium-tuberculosis-phagocytized-by-thp-1%C3%A2-cell-lines
#5
Alireza Jafari, Nader Mosavari, Farahnaz Movahedzadeh, Saeedeh Jafari Nodooshan, Roya Safarkar, Rossella Moro, Morteza Kamalzadeh, Ali Majidpour, Mina Boustanshenas, Tahereh Mosavi
The purpose of this research project was to infection of human macrophages (THP-1) cell lines by H37Rv strain of Mycobacterium tuberculosis (H37RvMTB) and find out the ratio/dilution of mixture silver (Ag NPs) and zinc oxide nanoparticles (ZnO NPs) whose ability to eliminate phagocytized bacteria compared to rifampicin. The colloidal Ag NPs and ZnO NPs were synthesized and their characteristics were evaluated. The THP-1 cell lines were infected with different concentration of H37RvMTB. Next, the infected cells were treated with different ratios/dilutions of Ag NPs, ZnO NPs and rifampicin...
July 11, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28707004/host-sirtuin-1-regulates-mycobacterial-immunopathogenesis-and-represents-a-therapeutic-target-against-tuberculosis
#6
Catherine Y Cheng, Nuria M Gutierrez, Mardiana B Marzuki, Xiaohua Lu, Taylor W Foreman, Bhairav Paleja, Bernett Lee, Akhila Balachander, Jinmiao Chen, Liana Tsenova, Natalia Kurepina, Karen W W Teng, Kim West, Smriti Mehra, Francesca Zolezzi, Michael Poidinger, Barry Kreiswirth, Deepak Kaushal, Hardy Kornfeld, Evan W Newell, Amit Singhal
Mycobacterium tuberculosis (Mtb) executes a plethora of immune-evasive mechanisms, which contribute to its pathogenesis, limited efficacy of current therapy, and the emergence of drug-resistant strains. This has led to resurgence in attempts to develop new therapeutic strategies/targets against tuberculosis (TB). We show that Mtb down-regulates sirtuin 1 (SIRT1), a nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase, in monocytes/macrophages, TB animal models, and TB patients with active disease...
March 2017: Science Immunology
https://www.readbyqxmd.com/read/28704501/reduced-susceptibility-of-clinical-strains-of-mycobacterium-tuberculosis-to-reactive-nitrogen-species-promotes-survival-in-activated-macrophages
#7
Jonna Idh, Blanka Andersson, Maria Lerm, Johanna Raffetseder, Daniel Eklund, Hanna Woksepp, Jim Werngren, Mikael Mansjö, Tommy Sundqvist, Olle Stendahl, Thomas Schön
BACKGROUND: Drugs such as isoniazid (INH) and pretomanid (PRT), used against Mycobacterium tuberculosis are active partly through generation of reactive nitrogen species (RNS). The aim of this study was to explore variability in intracellular susceptibility to nitric oxide (NO) in clinical strains of M. tuberculosis. METHOD: Luciferase-expressing clinical M. tuberculosis strains with or without INH resistance were exposed to RNS donors (DETA/NO and SIN-1) in broth cultures and bacterial survival was analysed by luminometry...
2017: PloS One
https://www.readbyqxmd.com/read/28695899/innate-scavenger-receptor-a-regulates-adaptive-t-helper-cell-responses-to-pathogen-infection
#8
Zhipeng Xu, Lei Xu, Wei Li, Xin Jin, Xian Song, Xiaojun Chen, Jifeng Zhu, Sha Zhou, Yong Li, Weiwei Zhang, Xiaoxiao Dong, Xiaowei Yang, Feng Liu, Hui Bai, Qi Chen, Chuan Su
The pattern recognition receptor (PRR) scavenger receptor class A (SR-A) has an important function in the pathogenesis of non-infectious diseases and in innate immune responses to pathogen infections. However, little is known about the role of SR-A in the host adaptive immune responses to pathogen infection. Here we show with mouse models of helminth Schistosoma japonicum infection and heat-inactivated Mycobacterium tuberculosis stimulation that SR-A is regulated by pathogens and suppresses IRF5 nuclear translocation by direct interaction...
July 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28693442/evaluation-of-the-relationship-between-marco-and-cd36-single-nucleotide-polymorphisms-and-susceptibility-to-pulmonary-tuberculosis-in-a-chinese-han-population
#9
Wenting Lao, Hui Kang, Guojiang Jin, Li Chen, Yang Chu, Jiao Sun, Bingqi Sun
BACKGROUND: Gene polymorphisms impact greatly on a person's susceptibility to pulmonary tuberculosis (PTB). Macrophage receptor with collagenous structure (MARCO) and CD36 are two scavenger receptors (SRs) that can recognize Mycobacterium tuberculosis (Mtb) and play a key role in tuberculosis infection. Gene polymorphisms of MARCO and CD36 may contribute to tuberculosis risk. METHODS: To investigate whether genetic polymorphisms of MARCO and CD36 are associated with susceptibility to PTB, genomic DNA samples from patients (n = 202) and healthy controls (n = 216) were collected and analyzed by polymerase chain reaction with high-resolution melting analysis...
July 11, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28689009/survival-of-mycobacterium-tuberculosis-and-mycobacterium-bovis-bcg-in-lysosomes-in%C3%A2-vivo
#10
Varadharajan Sundaramurthy, Hannelie Korf, Ashima Singla, Nicole Scherr, Liem Nguyen, Giorgio Ferrari, Regine Landmann, Kris Huygen, Jean Pieters
Mycobacterium tuberculosis is one of the most successful pathogens known, having infected more than a third of the global population. An important strategy for intracellular survival of pathogenic mycobacteria relies on their capacity to resist delivery to lysosomes, instead surviving within macrophage phagosomes. Several factors of both mycobacterial and host origin have been implicated in this process. However, whether or not this strategy is employed in vivo is not clear. Here we show that in vivo, following intravenous infection, M...
July 6, 2017: Microbes and Infection
https://www.readbyqxmd.com/read/28671529/mycobacterium-tuberculosis-hypoxic-response-protein-1-hrp1-augments-the-pro-inflammatory-response-and-enhances-the-survival-of-mycobacterium-smegmatis-in-murine-macrophages
#11
Changfeng Sun, Guoping Yang, Jinning Yuan, Xuan Peng, Chunxi Zhang, Xiaoqian Zhai, Tao Luo, Lang Bao
PURPOSE: The DosR/DosS two-component regulatory system of Mycobacterium tuberculosis regulates the expression of numerous genes under stress conditions and is important for the long-term survival of M. tuberculosis in the host. The rv2626c gene of M. tuberculosis is one of the most strongly induced transcripts of the dormancy regulon. This study focused on the immunological effects and possible function of Rv2626c in maintaining mycobacterial survival under various stress conditions. METHODOLOGY: We heterologously expressed the Rv2626c protein in Mycobacterium smegmatis by constructing a recombinant strain Ms_rv2626c...
July 3, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28669623/dual-antibiotherapy-of-tuberculosis-mediated-by-inhalable-locust-bean-gum-microparticles
#12
Susana Rodrigues, Ana D Alves, Joana S Cavaco, Jorge F Pontes, Filipa Guerreiro, Ana M Rosa da Costa, Francesca Buttini, Ana Grenha
Despite the existence of effective oral therapy, tuberculosis remains a deadly pathology, namely because of bacterial resistance and incompliance with treatments. Establishing alternative therapeutic approaches is urgently needed and inhalable therapy has a great potential in this regard. As pathogenic bacteria are hosted by alveolar macrophages, the co-localisation of antitubercular drugs and pathogens is thus potentiated by this strategy. This work proposes inhalable therapy of pulmonary tuberculosis mediated by a single locust bean gum (LBG) formulation of microparticles associating both isoniazid and rifabutin, complying with requisites of the World Health Organisation of combined therapy...
June 29, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28658262/mycobacteria-induce-tpl-2-mediated-il-10-in-il-4-generated-alternatively-activated-macrophages
#13
Soumya Chatterjee, Kawsar R Talaat, Emily E van Seventer, Carl G Feng, Alan L Scott, Anne Jedlicka, Amanda Dziedzic, Thomas B Nutman
IL-4 drives expansion of Th2 cells that cause generation of alternatively activated macrophages (AAMs). Filarial infections are established early in life, induce increased IL-4 production are co-endemic with tuberculosis (TB). We sought to understand, therefore, how mycobacteria are handled in the context of IL-4-induced AAM. Comparing IL-4 generated in vitro monocyte derived human AAMs to LPS and IFN-γ generated classically macrophages (CAMs), both infected with mycobacteria (BCG), we demonstrated increased early BCG uptake and increased IL-10 production in AAMs compared to CAMs...
2017: PloS One
https://www.readbyqxmd.com/read/28654200/preparation-and-evaluation-of-potent-pentafluorosulfanyl-substituted-anti-tuberculosis-compounds
#14
Garrett C Moraski, Ryan Bristol, Natalie Seeger, Helena I Boshoff, Patricia Siu-Yee Tsang, Marvin J Miller
The global fight to stop tuberculosis (TB) remains a great challenge, particularly with the increase in drug-resistant strains and a lack of funding to support the development of new treatments. To bolster a precarious drug pipeline, we prepared a focused panel of eight pentafluorosulfanyl (SF5 ) compounds which were screened for their activity against Mycobacterium tuberculosis (Mtb) H37Rv in three different assay conditions and media. All eight compounds had sub-micromolar potency, and four displayed MICs <100 nm...
June 27, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28648687/nramp1-d543n-and-int4-polymorphisms-in-susceptibility-to-pulmonary-tuberculosis-a-meta-analysis
#15
Leyong Yuan, Zunqiong Ke, Yi Guo, Xueyan Xi, Zhiguo Luo
The association of natural resistance associated macrophage protein 1 (NRAMP1) polymorphisms (D543N, INT4) with pulmonary tuberculosis (PTB) risk have been widely reported. However, the findings of previous studies were inconsistent. To clarify the role of these polymorphisms in PTB, we performed a meta-analysis of all available and relevant published studies. Based on comprehensive searches of the PubMed, Medline, Embase, Web of Science, Elsevier Science Direct and Cochrane Library database, we identified outcome data from all articles estimating the association between NRAMP1 polymorphisms and PTB risk...
June 22, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28646367/ifn%C3%AE-producing-cd4-t-lymphocytes-the-double-edged-swords-in-tuberculosis
#16
Pawan Kumar
IFNγ-producing CD4(+) T cells (IFNγ(+)CD4(+) T cells) are the key orchestrators of protective immunity against Mycobacterium tuberculosis (Mtb). Primarily, these cells act by enabling Mtb-infected macrophages to enforce phagosome-lysosome fusion, produce reactive nitrogen intermediates (RNIs), and activate autophagy pathways. However, TB is a heterogeneous disease and a host of clinical and experimental findings has also implicated IFNγ(+)CD4(+) T cells in TB pathogenesis. High frequency of IFNγ(+)CD4(+) T cells is the most invariable feature of the active disease...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28642632/mcl-plays-an-anti-inflammatory-role-in-mycobacterium-tuberculosis-induced-immune-response-by-inhibiting-nf-%C3%AE%C2%BAb-and-nlrp3-inflammasome-activation
#17
Qingwen Zhang, Xinru Jiang, Weigang He, Kailin Wei, Jinxia Sun, Xiangyang Qin, Yuejuan Zheng, Xin Jiang
Mycobacterium tuberculosis (Mtb) remains a significant menace to global health as it induces granulomatous lung lesions and systemic inflammatory responses during active tuberculosis (TB). Micheliolide (MCL), a sesquiterpene lactone, was recently reported to have a function of relieving LPS-induced inflammatory response, but the regulative role of MCL on the immunopathology of TB still remains unknown. In this experiment, we examined the inhibitory effect of MCL on Mtb-induced inflammatory response in mouse macrophage-like cell line Raw264...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28636635/microrna-144-3p-inhibits-autophagy-activation-and-enhances-bacillus-calmette-gu%C3%A3-rin-infection-by-targeting-atg4a-in-raw264-7-macrophage-cells
#18
Le Guo, Linlin Zhou, Qian Gao, Aijun Zhang, Jun Wei, Dantong Hong, Yuankui Chu, Xiangguo Duan, Ying Zhang, Guangxian Xu
MicroRNAs (miRNAs) are small noncoding nucleotides that play major roles in the response of host immune cells. Autophagy plays a key role in activating the antimicrobial host defense against Mycobacterium tuberculosis (M. tuberculosis). Whether miRNAs specifically influence the activation of macrophage autophagy during M. tuberculosis infection is largely unknown. In the present study, we demonstrate that Mycobacterium bovis Bacillus Calmette-Guérin (BCG) infection of macrophages leads to increased expression of miR-144-3p, which targets autophagy-related gene 4a (ATG4a), to inhibit autophagy activation and antimicrobial responses to BCG...
2017: PloS One
https://www.readbyqxmd.com/read/28634479/whole-blood-profiling-of-bacillus-calmette-gu%C3%A3-rin-induced-trained-innate-immunity-in-infants-identifies-epidermal-growth-factor-il-6-platelet-derived-growth-factor-ab-bb-and-natural-killer-cell-activation
#19
Steven G Smith, Johanneke Kleinnijenhuis, Mihai G Netea, Hazel M Dockrell
Vaccination of infants with bacillus Calmette-Guérin (BCG) activates both the innate and adaptive arms of the immune response. The antimycobacterial effects of these responses most likely account for the ability of BCG to protect against childhood forms of tuberculosis (TB). There is also evidence for a heterologous protective effect of BCG vaccination against TB-unrelated mortality in low birth weight infants. A possible mechanism of action of this effect, the induction of trained innate immunity, has been demonstrated when cells from BCG-vaccinated adults are restimulated in vitro with non-related microbial stimuli...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28630063/listeria-vectored-vaccine-expressing-the-mycobacterium-tuberculosis-30-kda-major-secretory-protein-via-the-constitutively-active-prfa-regulon-boosts-bcg-efficacy-against-tuberculosis
#20
Qingmei Jia, Barbara Jane Dillon, Saša Masleša-Galić, Marcus A Horwitz
A potent vaccine against tuberculosis, one of the world's deadliest diseases, is needed to enhance the immunity of people worldwide, most of whom have been vaccinated with the partially effective BCG vaccine. Here we investigate novel live attenuated recombinant Listeria monocytogenes (rLm) vaccines expressing the Mycobacterium tuberculosis (Mtb) 30 kDa major secretory protein (r30/Ag85B) (rLm30) as heterologous booster vaccines in animals primed with BCG. Using three attenuated Lm vectors, rLm ΔactA (LmI), rLm ΔactA ΔinlB (LmII), and rLm ΔactA ΔinlBprfA* (LmIII), we constructed five rLm30 vaccine candidates expressing the r30 linked in-frame to the Lm Listeriolycin O signal sequence and driven by the hly promoter (h30) or linked in-frame to the ActA N-terminus and driven by the actA promoter (a30)...
June 19, 2017: Infection and Immunity
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