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https://www.readbyqxmd.com/read/30338218/the-amino-terminal-domain-of-mycobacterium-tuberculosis-clpb-protein-plays-a-crucial-role-in-its-substrate-disaggregation-activity
#1
Prajna Tripathi, Priyanka Parijat, Virendra Kumar Patel, Janendra K Batra
Mycobacterium tuberculosis ( Mtb ) is known to persist in extremely hostile environments within host macrophages. The ability to withstand such proteotoxic stress comes from its highly conserved molecular chaperone machinery. ClpB, a unique member of the AAA+ family of chaperones, is responsible for resolving aggregates in Mtb and many other bacterial pathogens. Mtb produces two isoforms of ClpB, a full length and an N-terminally truncated form (ClpB∆N), with the latter arising from an internal translation initiation site...
October 2018: FEBS Open Bio
https://www.readbyqxmd.com/read/30337468/-mycobacterium-tuberculosis-induced-ifn-%C3%AE-production-requires-cytosolic-dna-and-rna-sensing-pathways
#2
Yong Cheng, Jeffrey S Schorey
RNA sensing pathways are key elements in a host immune response to viral pathogens, but little is known of their importance during bacterial infections. We found that Mycobacterium tuberculosis ( M.tb ) actively releases RNA into the macrophage cytosol using the mycobacterial SecA2 and ESX-1 secretion systems. The cytosolic M.tb RNA induces IFN-β production through the host RIG-I/MAVS/IRF7 RNA sensing pathway. The inducible expression of IRF7 within infected cells requires an autocrine signaling through IFN-β and its receptor, and this early IFN-β production is dependent on STING and IRF3 activation...
October 18, 2018: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/30333800/heparin-binding-hemagglutinin-adhesin-hbha-is-involved-in-intracytosolic-lipid-inclusions-formation-in-mycobacteria
#3
Dominique Raze, Claudie Verwaerde, Gaspard Deloison, Elisabeth Werkmeister, Baptiste Coupin, Marc Loyens, Priscille Brodin, Carine Rouanet, Camille Locht
The heparin-binding hemagglutinin adhesin (HBHA) is an important virulence factor of Mycobacterium tuberculosis . It is a surface-displayed protein that serves as an adhesin for non-phagocytic cells and is involved in extra-pulmonary dissemination of the tubercle bacillus. It is also an important latency antigen useful for the diagnosis of latently M. tuberculosis -infected individuals. Using fluorescence time-lapse microscopy on mycobacteria that produce HBHA-green fluorescent protein chimera, we show here that HBHA can be found at two different locations and dynamically alternates between the mycobacterial surface and the interior of the cell, where it participates in the formation of intracytosolic lipid inclusions (ILI)...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/30327492/publisher-correction-mycobacterium-tuberculosis-carrying-a-rifampicin-drug-resistance-mutation-reprograms-macrophage-metabolism-through-cell-wall-lipid-changes
#4
Nicole C Howard, Nancy D Marin, Mushtaq Ahmed, Bruce A Rosa, John Martin, Monika Bambouskova, Alexey Sergushichev, Ekaterina Loginicheva, Natalia Kurepina, Javier Rangel-Moreno, Liang Chen, Barry N Kreiswirth, Robyn S Klein, Joan-Miquel Balada-Llasat, Jordi B Torrelles, Gaya K Amarasinghe, Makedonka Mitreva, Maxim N Artyomov, Fong-Fu Hsu, Barun Mathema, Shabaana A Khader
In the version of this Letter originally published, in Fig. 2d, in the third graph, the label for the y axis was incorrect as 'TNF-α (pg ml-1 )'; it should have read 'IL-1β (pg ml-1 )'. This has now been corrected.
October 16, 2018: Nature Microbiology
https://www.readbyqxmd.com/read/30327467/microrna-27a-controls-the-intracellular-survival-of-mycobacterium-tuberculosis-by-regulating-calcium-associated-autophagy
#5
Feng Liu, Jianxia Chen, Peng Wang, Haohao Li, Yilong Zhou, Haipeng Liu, Zhonghua Liu, Ruijuan Zheng, Lin Wang, Hua Yang, Zhenling Cui, Fei Wang, Xiaochen Huang, Jie Wang, Wei Sha, Heping Xiao, Baoxue Ge
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills millions every year, and there is urgent need to develop novel anti-TB agents due to the fast-growing of drug-resistant TB. Although autophagy regulates the intracellular survival of Mtb, the role of calcium (Ca2+ ) signaling in modulating autophagy during Mtb infection remains largely unknown. Here, we show that microRNA miR-27a is abundantly expressed in active TB patients, Mtb-infected mice and macrophages. The target of miR-27a is the ER-located Ca2+ transporter CACNA2D3...
October 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/30326918/upregulation-of-mir-196b-5p-attenuates-bcg-uptake-via-targeting-socs3-and-activating-stat3-in-macrophages-from-patients-with-long-term-cigarette-smoking-related-active-pulmonary-tuberculosis
#6
Yaoqin Yuan, Dongzi Lin, Long Feng, Mingyuan Huang, Huimin Yan, Yumei Li, Yinwen Chen, Bihua Lin, Yan Ma, Ziyu Ye, Yuezhi Mei, Xiaolin Yu, Keyuan Zhou, Qunzhou Zhang, Tao Chen, Jincheng Zeng
BACKGROUND: Cigarette smoking (CS) triggers an intense and harmful inflammatory response in lungs mediated by alveolar and blood macrophages, monocytes, and neutrophils and is closely associated with prevalence of tuberculosis (TB). The risk of death in patients with long-term cigarette smoking-related pulmonary tuberculosis (LCS-PTB) is approximately 4.5 times higher than those with nonsmoking pulmonary tuberculosis (N-PTB). However, the mechanisms underlying the harmful inflammatory responses in the setting of LCS-PTB have not been well documented...
October 16, 2018: Journal of Translational Medicine
https://www.readbyqxmd.com/read/30320743/identification-of-virulence-markers-of-mycobacterium-abscessus-for-intracellular-replication-in-phagocytes
#7
Violaine Dubois, Laura Laencina, Anouchka Bories, Vincent Le Moigne, Alexandre Pawlik, Jean-Louis Herrmann, Fabienne Girard-Misguich
What differentiates Mycobacterium abscessus from other saprophytic mycobacteria is the ability to resist phagocytosis by human macrophages and the ability to multiply inside such cells. These virulence traits render M. abscessus pathogenic, especially in vulnerable hosts with underlying structural lung disease, such as cystic fibrosis, bronchiectasis or tuberculosis. How patients become infected with M. abscessus remains unclear. Unlike many mycobacteria, M. abscessus is not found in the environment but might reside inside amoebae, environmental phagocytes that represent a potential reservoir for M...
September 27, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/30319650/il-22-an-underestimated-player-in-natural-resistance-to-tuberculosis
#8
REVIEW
Katharina Ronacher, Roma Sinha, Michelle Cestari
Approximately 10% of individuals latently infected with Mycobacterium tuberculosis (Mtb) develop active tuberculosis (TB) during their lifetime. Although it is well recognized that T-helper 1 immune responses are crucial for containing latent TB infection, the full array of host factors conferring protective immunity from TB progression are not completely understood. IL-22 is produced by cells of the innate and adaptive immune system including innate lymphoid cells, and natural killer cells as well as T lymphocytes (Th1, Th17, and Th22) and binds to its cognate receptor, the IL-22R1, which is expressed on non-hematopoietic cells such as lung epithelial cells...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30319611/rv3033-as-an-emerging-anti-apoptosis-factor-facilitates-mycobacteria-survival-via-inhibiting-macrophage-intrinsic-apoptosis
#9
Wei Zhang, Qian Lu, Yuanshu Dong, Yan Yue, Sidong Xiong
Apoptosis inhibition is a critical strategy of mycobacteria facilitating its survival in macrophages, but the underlying mechanism is not completely understood. In this study, we found that Rv3033, a secreted virulence factor of mycobacteria, played an important role in bacillary survival within macrophages. Forced over-expressed of Rv3033 in macrophages could efficiently resist mycobacteria-induced early and late apoptosis, accompanied with the obvious increased cellular bacterial burden. By exploring the underlying mechanism, we found that Rv3033 efficiently repressed the intrinsic (caspase-9 meditated), but not the extrinsic (caspase-8 mediated) apoptotic pathway in mycobacteria-infected macrophages...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30317660/phospholipase-c-%C3%AE-2-promotes-intracellular-survival-of-mycobacteria
#10
Ruchi Paroha, Shivendra K Chaurasiya, Rashmi Chourasia
Mycobacterium tuberculosis (Mtb) infects millions of people each year. These bacilli can survive inside macrophages. To favor their survival, pathogen alters various signal transduction pathways in host cells. Phospholipase C (PLC) signaling regulates various processes in mammalian cells but has never been investigated for their roles in regulating phagocytosis and killing of mycobacteria by macrophages. Here, we report that infection with Mtb but not Mycobacterium smegmatis (MS) induces phosphorylation of PLC-γ2 at tyrosine 1217 in J774A...
October 14, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/30317025/novel-indole-thiazolidinone-conjugates-design-synthesis-and-whole-cell-phenotypic-evaluation-as-a-novel-class-of-antimicrobial-agents
#11
Mahmoud F Abo-Ashour, Wagdy M Eldehna, Riham F George, Marwa M Abdel-Aziz, Mahmoud M Elaasser, Nagwa M Abdel Gawad, Antima Gupta, Sanjib Bhakta, Sahar M Abou-Seri
In connection with our research program on the development of novel anti-tubercular candidates, herein we report the design and synthesis of two different sets of indole-thiazolidinone conjugates (8a,b; 11a-d) and (14a-k; 15a-h). The target compounds were evaluated for their in vitro antibacterial and antifungal activities against selected human pathogens viz. Staphylococcus aureus (Gram positiveve), Pseudomonas aeruginosa, Escherichia coli (Gram negative), Mycobacterium tuberculosis (Acid-fast bacteria), Aspergillus fumigates and Candida albicans (fungi)...
October 4, 2018: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/30306257/macrophage-microbe-interaction-lessons-learned-from-the-pathogen-mycobacterium-tuberculosis
#12
REVIEW
Somdeb BoseDasgupta, Jean Pieters
Macrophages, being the cornerstone of the immune system, have adapted the ancient nutrient acquisition mechanism of phagocytosis to engulf various infectious organisms thereby helping to orchestrate an appropriate host response. Phagocytosis refers to the process of internalization and degradation of particulate material, damaged and senescent cells and microorganisms by specialized cells, after which the vesicle containing the ingested particle, the phagosome, matures into acidic phagolysosomes upon fusion with hydrolytic enzyme-containing lysosomes...
October 10, 2018: Seminars in Immunopathology
https://www.readbyqxmd.com/read/30301850/arylvinylpiperazine-amides-a-new-class-of-potent-inhibitors-targeting-qcrb-of-mycobacterium-tuberculosis
#13
Caroline S Foo, Andréanne Lupien, Maryline Kienle, Anthony Vocat, Andrej Benjak, Raphael Sommer, Dirk A Lamprecht, Adrie J C Steyn, Kevin Pethe, Jérémie Piton, Karl-Heinz Altmann, Stewart T Cole
New drugs are needed to control the current tuberculosis (TB) pandemic caused by infection with Mycobacterium tuberculosis We report here on our work with AX-35, an arylvinylpiperazine amide, and four related analogs, which are potent antitubercular agents in vitro All five compounds showed good activity against M. tuberculosis in vitro and in infected THP-1 macrophages, while displaying only mild cytotoxicity. Isolation and characterization of M. tuberculosis -resistant mutants to the arylvinylpiperazine amide derivative AX-35 revealed mutations in the qcrB gene encoding a subunit of cytochrome bc 1 oxidase, one of two terminal oxidases of the electron transport chain...
October 9, 2018: MBio
https://www.readbyqxmd.com/read/30301802/mmpl8-mab-controls-mycobacterium-abscessus-virulence-and-production-of-a-previously-unknown-glycolipid-family
#14
Violaine Dubois, Albertus Viljoen, Laura Laencina, Vincent Le Moigne, Audrey Bernut, Faustine Dubar, Mickaël Blaise, Jean-Louis Gaillard, Yann Guérardel, Laurent Kremer, Jean-Louis Herrmann, Fabienne Girard-Misguich
Mycobacterium abscessus is a peculiar rapid-growing Mycobacterium (RGM) capable of surviving within eukaryotic cells thanks to an arsenal of virulence genes also found in slow-growing mycobacteria (SGM), such as Mycobacterium tuberculosis A screen based on the intracellular survival in amoebae and macrophages (MΦ) of an M. abscessus transposon mutant library revealed the important role of MAB_0855, a yet uncharacterized Mycobacterial membrane protein Large (MmpL). Large-scale comparisons with SGM and RGM genomes uncovered MmpL12 proteins as putative orthologs of MAB_0855 and a locus-scale synteny between the MAB_0855 and Mycobacterium chelonae mmpL8 loci...
October 9, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/30292819/biochemical-and-structural-characterization-of-tesa-a-major-thioesterase-required-for-outer-envelope-lipid-biosynthesis-in-mycobacterium-tuberculosis
#15
Phuong Chi Nguyen, Van Son Nguyen, Benjamin P Martin, Patrick Fourquet, Luc Camoin, Chistopher D Spilling, Jean-François Cavalier, Christian Cambillau, Stéphane Canaan
With the high number of patients infected by tuberculosis and the sharp increase of drug-resistant tuberculosis cases, developing new drugs to fight this disease has become increasingly urgent. In this context, analogs of the naturally occurring enolphosphates Cyclipostins and Cyclophostin (CyC analogs) offer new therapeutic opportunities. The CyC analogs display potent activity both in vitro and in infected macrophages against several pathogenic mycobacteria including Mycobacterium tuberculosis and Mycobacterium abscessus...
October 4, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/30290883/calcitriol-increases-nitric-oxide-production-and-modulates-microbicidal-capacity-against-mycobacterium-bovis-in-bovine-macrophages
#16
Ángel García-Barragán, José A Gutiérrez-Pabello, Edgar Alfonseca-Silva
Bovine tuberculosis, a re-emerging infectious disease caused by Mycobacterium bovis, can be transmitted to humans. Global prevalence of M. bovis in humans is underestimated and represents a serious public health risk in developing countries. In light of this situation, it is important to note that our understanding of the immunopathogenesis of human tuberculosis can be improved by studying this disease in the bovine model. Stimulation of the bovine innate immune system with calcitriol (1,25(OH)2D3) leads to an increase in bactericidal molecules involved in macrophage antimicrobial activity...
August 2018: Comparative Immunology, Microbiology and Infectious Diseases
https://www.readbyqxmd.com/read/30289942/correction-improved-control-of-tuberculosis-and-activation-of-macrophages-in-mice-lacking-protein-kinase-r
#17
Kangyun Wu, Jovanka Koo, Xiuju Jiang, Ran Chen, Stanley N Cohen, Carl Nathan
[This corrects the article DOI: 10.1371/journal.pone.0030512.].
2018: PloS One
https://www.readbyqxmd.com/read/30288253/phagocytosis-influences-the-intracellular-survival-of-mycobacterium-smegmatis-via-the-endoplasmic-reticulum-stress-response
#18
Seon-Hwa Kim, Soo-Na Cho, Yun-Ji Lim, Ji-Ae Choi, Junghwan Lee, Dam Go, Chang-Hwa Song
Background: Mycobacterium smegmatis , a rapidly growing non-tuberculosis mycobacterium, is a good model for studying the pathogenesis of tuberculosis because of its genetic similarity to Mycobacterium tuberculosis (Mtb). Macrophages remove mycobacteria during an infection. Macrophage apoptosis is a host defense mechanism against intracellular bacteria. We have reported that endoplasmic reticulum (ER) stress is an important host defense mechanism against Mtb infection. Results: In this study, we found that M...
2018: Cell & Bioscience
https://www.readbyqxmd.com/read/30287353/over-expression-of-the-constitutive-expression-refractory-mycobacterium-tuberculosis-rv3488-protein-with-an-acid-inducible-expression-system
#19
Nam Pham, Nelson Dao, Beatrice Saviola
As inducible protein expression plasmids available for mycobacterial species are limited, here we demonstrate the utility of an acid-inducible promoter driving gene and subsequent protein expression of a difficult to express protein. We wanted to assess the use of an acid inducible promoter expression system to produce proteins in a mycobacterial system, specifically proteins that when overexpressed interfere with mycobacterial cell growth. Overexpression of those types of proteins would require a tightly regulated promoter system...
October 1, 2018: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/30283745/-mycobacterium-tuberculosis-virulent-factor-esat-6-drives-macrophage-differentiation-toward-the-pro-inflammatory-m1-phenotype-and-subsequently-switches-it-to-the-anti-inflammatory-m2-phenotype
#20
Amira Refai, Sami Gritli, Mohamed-Ridha Barbouche, Makram Essafi
Tuberculosis, a human infectious disease caused by Mycobacterium tuberculosis ( M.tb ), is still a major cause of morbidity and mortality worldwide. The success of M.tb as a pathogen relies mainly on its ability to divert the host innate immune responses. One way by which M.tb maintains a persistent infection in a "silent" granuloma is to inhibit inflammation and induce an immunoregulatory phenotype in host macrophages (MΦs). However, M.tb effectors governing the switch of MΦs from the pro-inflammatory M1 to the anti-inflammatory M2 phenotype remain to be determined...
2018: Frontiers in Cellular and Infection Microbiology
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