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https://www.readbyqxmd.com/read/28819202/mechanism-of-transformation-in-mycobacteria-using-a-novel-shockwave-assisted-technique-driven-by-in-situ-generated-oxyhydrogen
#1
Akshay Datey, Janardhanraj Subburaj, Jagadeesh Gopalan, Dipshikha Chakravortty
We present a novel method for shockwave-assisted bacterial transformation using a miniature oxyhydrogen detonation-driven shock tube. We have obtained transformation efficiencies of about 1.28 × 10(6), 1.7 × 10(6), 5 × 10(6), 1 × 10(5), 1 × 10(5) and 2 × 10(5) transformants/µg of DNA for Escherichia coli, Salmonella Typhimurum, Pseudomonas aeruginosa, Mycobacterium smegmatis, Mycobacterium tuberculosis (Mtb) and Helicobacter pylori respectively using this method which are significantly higher than those obtained using conventional methods...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28811474/the-mycobacterial-phosphatase-ptpa-regulates-the-expression-of-host-genes-and-promotes-cell-proliferation
#2
Jing Wang, Pupu Ge, Lihua Qiang, Feng Tian, Dongdong Zhao, Qiyao Chai, Mingzhao Zhu, Rongbin Zhou, Guangxun Meng, Yoichiro Iwakura, George Fu Gao, Cui Hua Liu
Mycobacterium tuberculosis PtpA is a secreted effector protein that dephosphorylates several proteins in the host cell cytoplasm, such as p-JNK, p-p38, and p-VPS33B, leading to suppression of host innate immunity. Here we show that, in addition, PtpA enters the nucleus of host cells and regulates the expression of host genes, some of which are known to be involved in host innate immunity or in cell proliferation and migration (such as GADD45A). PtpA can bind directly to the promoter region of GADD45A in vitro...
August 15, 2017: Nature Communications
https://www.readbyqxmd.com/read/28810868/nontuberculosis-mycobacteria-are-the-major-causes-of-tuberculosis-like-lesions-in-cattle-slaughtered-at-bahir-dar-abattoir-northwestern-ethiopia
#3
Anwar Nuru, Aboma Zewude, Temesgen Mohammed, Biniam Wondale, Laikemariam Teshome, Muluwork Getahun, Gezahegne Mamo, Girmay Medhin, Rembert Pieper, Gobena Ameni
BACKGROUND: The main cause of bovine tuberculosis (bTB) is believed to be Mycobacterium bovis (M. bovis). Nontuberculosis mycobacteria (NTM) are neglected but opportunistic pathogens and obstacles for bTB diagnosis. This study aimed to isolate and characterize the mycobacteria organisms involved in causing TB-like lesions in cattle in northwestern Ethiopia. RESULTS: A total of 2846 carcasses of cattle were inspected for TB lesions. Ninety six tissues (including lymph nodes such as submandibular, retropharyngeal, tonsilar, mediatinal, bronchial and mesenteric, and organs such as lung, liver and kidney) with suspicious TB lesion(s) were collected and cultured on Lowenstein-Jensen medium...
August 15, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28807911/systematic-review-and-meta-analyses-of-the-effect-of-chemotherapy-on-pulmonary-mycobacterium-abscessus-outcomes-and-disease-recurrence
#4
Jotam G Pasipanodya, Deborah Ogbonna, Beatriz E Ferro, Gesham Magombedze, Shashikant Srivastava, Devyani Deshpande, Tawanda Gumbo
Background. In pharmacokinetic/pharmacodynamics models of pulmonary Mycobacterium abscessus complex, the recommended macrolide-containing combination therapy has poor kill rates. However, clinical outcomes are unknown.Methods We searched the literature for studies published between 1990-2017 that reported microbial outcomes in patients treated for pulmonary M. abscessus disease. Good outcome was defined as sustained sputum culture conversion (SSCC) without relapse. Random effects models were used to pool studies and estimate proportions of patients with good outcomes...
August 14, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28806050/linking-high-throughput-screens-to-identify-moas-and-novel-inhibitors-of-mycobacterium-tuberculosis-dihydrofolate-reductase
#5
John P Santa Maria, Yumi Park, Lihu Yang, Nicholas Murgolo, Michael D Altman, Paul Zuck, Greg Adam, Chad Chamberlin, Peter Saradjian, Peter Dandliker, Helena I M Boshoff, Clifton E Barry, Charles Garlisi, David B Olsen, Katherine Young, Meir Glick, Elliott Nickbarg, Peter S Kutchukian
Though phenotypic and target-based high-throughput screening approaches have been employed to discover new antibiotics, the identification of promising therapeutic candidates remains challenging. Each approach provides different information, and understanding their results can provide hypotheses for mechanism of action (MoA) and reveal actionable chemical matter. Here we describe a framework for identifying efficacy targets of bioactive compounds. High throughput biophysical profiling against a broad range of targets coupled with machine learning is employed to identify chemical features with predicted efficacy targets for a given phenotypic screen...
August 14, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28802398/a-mycobacterial-growth-inhibition-assay-mgia-for-bovine-tb-vaccine-development
#6
Ilaria Pepponi, Bhagwati Khatri, Rachel Tanner, Bernardo Villarreal-Ramos, Martin Vordermeier, Helen McShane
Human tuberculosis remains a significant cause of mortality and morbidity throughout the world. The global economic impact of bovine TB is considerable. An effective vaccine would be the most cost-effective way to control both epidemics, particularly in emerging economies. TB vaccine research would benefit from the identification of an immune correlate of protection with which vaccines could be gated at both preclinical and clinical levels. In-vitro mycobacterial growth inhibition assays (MGIA) are functional assays that include most aspects of the complex host immune response to mycobacteria, and they may serve as functional immune correlates for vaccine development...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28802397/lysx-gene-is-differentially-expressed-among-mycobacterium-tuberculosis-strains-with-different-levels-of-virulence
#7
Alejandra Montoya-Rosales, Roberta Provvedi, Flor Torres-Juarez, Jose A Enciso-Moreno, Rogelio Hernandez-Pando, Riccardo Manganelli, Bruno Rivas-Santiago
Antimicrobial peptides (AMPs) are mainly produced by epithelial cells and macrophages to eliminate infecting mycobacteria through direct antimicrobial activity and immunomodulation. Indeed, it has been described that this line of defense is essential to control infection. However, Mycobacterium tuberculosis (Mtb) has developed mechanisms to avoid AMPs activity, for instance lysX adds lysine residues to surface phospholipids changing their net charge, leading to the repelling of the AMPs. In the present study, we determined that lysX gene is differentially expressed among Mtb strains...
September 2017: Tuberculosis
https://www.readbyqxmd.com/read/28795999/the-utility-of-immunohistochemistry-in-mycobacterial-infection-a-proposal-for-multimodality-testing
#8
Isaac H Solomon, Melanie E Johncilla, Jason L Hornick, Danny A Milner
Mycobacterium species are slow growing bacteria that cause significant morbidity and mortality worldwide. Because of the relative rarity of mycobacterial infections, potential for detection of nonpathogenic environmental contaminants, and substantial costs associated with molecular diagnostics, effective screening methods are needed to identify samples most suitable for molecular testing. While anatomic pathology specimens can be utilized to identify characteristic histologic inflammatory patterns and to directly visualize mycobacteria through histochemical (acid fast bacilli [AFB]) stains, the utility of immunohistochemistry (IHC) in this setting is unknown...
August 8, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28776521/epidemiological-and-laboratorial-profile-of-patients-with-isolation-of-nontuberculous-mycobacteria
#9
Heloisa Silveira Paro Pedro, Andréa Gobetti Vieira Coelho, Isabela Mazuco Mansur, Ana Carolina Chiou, Maria Izabel Ferreira Pereira, Naiara Cristina Ule Belotti, Manuela Galloy Sanches Ismael, Maria Rita de Cássia Oliveira Cury, Susilene Maria Tonelli Nardi, Érica Chimara
BACKGROUND: An increase in NTM diseases in the international scenario has been observed in recent years. AIMS: To analyze the epidemiological and laboratory profiles of patients with isolation of nontuberculous mycobacteria (NTM) over one decade. A retrospective analysis of records of a mycobacterial reference laboratory found 135 cases with isolation of NTM. METHODS: Clinical and epidemiological data were collected from the records of government health clinics and from the State notification system (TBWEB)...
July 2017: International Journal of Mycobacteriology
https://www.readbyqxmd.com/read/28768708/identification-of-compounds-that-decrease-numbers-of-mycobacteria-in-human-macrophages-in-the-presence-of-serum-amyloid-p
#10
Wang Xiang, Nehemiah Cox, Richard H Gomer
Mϕs are a heterogeneous population of cells and include classically activated Mϕs (M1) and alternatively activated Mϕs (M2). Mϕs can change from M1 to M2 and vice versa in response to environmental stimuli. Serum amyloid P (SAP) is a constitutive plasma protein that polarizes Mϕs to an M2 phenotype, and part of this effect is mediated through FcγRI receptors. In an effort to find ways to alter Mϕs phenotypes, we screened for compounds that can block the SAP-FcγRI interaction. From a screen of 3000 compounds, we found 12 compounds that reduced the ability of fluorescently labeled human SAP to bind cells expressing human FcγRI...
August 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28767693/dendritic-cells-that-phagocytose-apoptotic-macrophages-loaded-with-mycobacterial-antigens-activate-cd8-t-cells-via-cross-presentation
#11
Patricia Espinosa-Cueto, Alejandro Magallanes-Puebla, Carlos Castellanos, Raul Mancilla
While homeostatic apoptosis is immunologically silent, macrophage apoptosis during Mycobacterium tuberculosis infection can potentially induce an immune response against the mycobacteria. To examine the role of dendritic cells in this response, macrophage apoptosis was induced by incubating the macrophage with cell wall extracts of mycobacteria expressing LpqH. The apoptogenic proteins of the cell wall extracts were engulfed by the macrophage and then were translocated from the cytosol to the nuclei of the dying cells...
2017: PloS One
https://www.readbyqxmd.com/read/28756649/rnomic-identification-and-evaluation-of-npctb_6715-a-non-protein-coding-rna-gene-as-a-potential-biomarker-for-the-detection-of-mycobacterium-tuberculosis
#12
Priyatharisni Kanniappan, Siti Aminah Ahmed, Ganeswrie Rajasekaram, Citartan Marimuthu, Ewe Seng Ch'ng, Li Pin Lee, Carsten A Raabe, Timofey S Rozhdestvensky, Thean Hock Tang
Technological advances in RNA biology greatly improved transcriptome profiling during the last two decades. Besides the discovery of many small RNAs (sRNA) that are involved in the physiological and pathophysiological regulation of various cellular circuits, it becomes evident that the corresponding RNA genes might also serve as potential biomarkers to monitor the progression of disease and treatment. sRNA gene candidate npcTB_6715 was previously identified via experimental RNomic (unpublished data), and we report its application as potential biomarker for the detection of Mycobacterium tuberculosis (MTB) in patient samples...
July 29, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28754952/mycobacterial-dna-binding-protein-1-is-critical-for-long-term-survival-of-mycobacterium-smegmatis-and-simultaneously-coordinates-cellular-functions
#13
Shymaa Enany, Yutaka Yoshida, Yoshitaka Tateishi, Yuriko Ozeki, Akihito Nishiyama, Anna Savitskaya, Takehiro Yamaguchi, Yukiko Ohara, Tadashi Yamamoto, Manabu Ato, Sohkichi Matsumoto
Bacteria can proliferate perpetually without ageing, but they also face conditions where they must persist. Mycobacteria can survive for a long period. This state appears during mycobacterial diseases such as tuberculosis and leprosy, which are chronic and develop after long-term persistent infections. However, the fundamental mechanisms of the long-term living of mycobacteria are unknown. Every Mycobacterium species expresses Mycobacterial DNA-binding protein 1 (MDP1), a histone-like nucleoid associated protein...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28750280/tuberculosis-vaccines-perspectives-from-the-nih-niaid-mycobacteria-vaccine-testing-program
#14
REVIEW
Angelo A Izzo
The development of novel vaccine candidates against infections with Mycobacterium tuberculosis has highlighted our limited understanding of immune mechanisms required to kill M. tuberculosis. The induction of a Th1 immunity is vital, but new studies are required to identify other mechanisms that may be necessary. Novel vaccines formulations that invoke effector cells such as innate lymphoid cells may provide an environment that promote effector mechanisms including T cell and B cell mediated immunity. Identifying pathways associated with killing this highly successful infectious agent has become critical to achieving the goal of reducing the global tuberculosis burden...
July 24, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28749330/in-vitro-activity-of-bedaquiline-against-rapidly-growing-nontuberculous-mycobacteria
#15
Diana A Aguilar-Ayala, Margo Cnockaert, Emmanuel André, Koen Andries, Jorge A Gonzalez-Y-Merchand, Peter Vandamme, Juan Carlos Palomino, Anandi Martin
Bedaquiline (BDQ) has been proven to be effective in the treatment of multidrug-resistant tuberculosis. We hypothesized that BDQ could be a potential agent to treat nontuberculous mycobacterial (NTM) infection. The objective of this study was to evaluate the in vitro activity of BDQ against rapidly growing mycobacteria by assessing the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) against 18 NTM strains. For MIC determination we performed the resazurin microtitre assay broth dilution, and for the MBC the c...
July 28, 2017: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/28748182/mycobacteria-modify-their-cell-size-control-under-sub-optimal-carbon-sources
#16
Miles Priestman, Philipp Thomas, Brian D Robertson, Vahid Shahrezaei
The decision to divide is the most important one that any cell must make. Recent single cell studies suggest that most bacteria follow an "adder" model of cell size control, incorporating a fixed amount of cell wall material before dividing. Mycobacteria, including the causative agent of tuberculosis Mycobacterium tuberculosis, are known to divide asymmetrically resulting in heterogeneity in growth rate, doubling time, and other growth characteristics in daughter cells. The interplay between asymmetric cell division and adder size control has not been extensively investigated...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28747346/modulation-of-roquin-function-in-myeloid-cells-reduces-mycobacterium-tuberculosis-induced-inflammation
#17
Gayathri Nagalingam, Carola G Vinuesa, Warwick J Britton, Bernadette M Saunders
Damaging inflammation is a hallmark of Mycobacterium tuberculosis infection, and understanding how this is regulated is important for the development of new therapies to limit excessive inflammation. The E3 ubiquitin ligase, Roquin, is involved in immune regulation; however, its role in immunity to M. tuberculosis is unknown. To address this, we infected mice with a point mutation in Roquin1/Rc3h1 (sanroque). Aerosol-infected sanroque mice showed enhanced control of M. tuberculosis infection associated with delayed bacterial dissemination and upregulated TNF production in the lungs after 2 wk...
July 26, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28744153/assessment-of-sputum-smear-positive-but-culture-negative-results-among-newly-diagnosed-pulmonary-tuberculosis-patients-in-tanzania
#18
Nicholaus Peter Mnyambwa, Esther S Ngadaya, Godfather Kimaro, Dong-Jin Kim, Rudovick Kazwala, Pammla Petrucka, Sayoki G Mfinanga
Diagnosis of pulmonary tuberculosis (TB) in technology-limited countries is widely achieved by smear microscopy, which has limited sensitivity and specificity. The frequency and clinical implication of smear-positive but culture-negative among presumptive TB patients remains unclear. A cross-sectional substudy was conducted which aimed to identify the proportion of nontuberculous mycobacteria (NTM) infections among 94 "smear-positive culture-negative" patients diagnosed between January 2013 and June 2016 in selected health facilities in Tanzania...
2017: International Journal of General Medicine
https://www.readbyqxmd.com/read/28739828/mice-bone-marrow-sca-1-cd44-mesenchymal-stem-cells-kill-avirulent-mycobacteria-but-not-mycobacterium-tuberculosis-through-modulation-of-cathelicidin-expression-via-p38-mapk-dependent-pathway
#19
Sumanta Kumar Naik, Avinash Padhi, Geetanjali Ganguli, Srabasti Sengupta, Sanghamitra Pati, Dasarathi Das, Avinash Sonawane
Mycobacterium tuberculosis (Mtb) primarily infects lung macrophages. However, recent study has shown that Mtb also infect and persist in dormant form inside the bone marrow mesenchymal stem cells (BM-MSCs) even after successful antibiotic therapy. However, the mechanism(s) by which Mtb survives in BM-MSCs is still not known. Like macrophages, BM-MSCs do not contain a well-defined endocytic pathway, which is known to play a central role in the clearance of internalized mycobacteria. Here, we studied the fate of virulent and avirulent mycobacteria in Sca-1(+)/CD44(+) BM-MSCs...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28727774/inhibitors-of-mycobacterium-marinum-virulence-identified-in-a-dictyostelium-discoideum-host-model
#20
Hajer Ouertatani-Sakouhi, Sébastien Kicka, Gianpaolo Chiriano, Christopher F Harrison, Hubert Hilbi, Leonardo Scapozza, Thierry Soldati, Pierre Cosson
Tuberculosis remains one of the major threats to public health worldwide. Given the prevalence of multi drug resistance (MDR) in Mycobacterium tuberculosis strains, there is a strong need to develop new anti-mycobacterial drugs with modes of action distinct from classical antibiotics. Inhibitors of mycobacterial virulence might target new molecular processes and may represent a potential new therapeutic alternative. In this study, we used a Dictyostelium discoideum host model to assess virulence of Mycobacterium marinum and to identify compounds inhibiting mycobacterial virulence...
2017: PloS One
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