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Mycobacterium complex

Pierre Santucci, Feriel Bouzid, Nabil Smichi, Isabelle Poncin, Laurent Kremer, Chantal De Chastellier, Michel Drancourt, Stéphane Canaan
Despite a slight decline since 2014, tuberculosis (TB) remains the major deadly infectious disease worldwide with about 1.5 million deaths each year and with about one-third of the population being latently infected with Mycobacterium tuberculosis, the etiologic agent of TB. During primo-infection, the recruitment of immune cells leads to the formation of highly organized granulomas. Among the different cells, one outstanding subpopulation is the foamy macrophage (FM), characterized by the abundance of triacylglycerol-rich lipid bodies (LB)...
2016: Frontiers in Cellular and Infection Microbiology
Shunjiro Noguchi, Yuko Nishimoto, Yoshio Taguchi, Yoichiro Kobashi, Satoshi Noma
No abstract text is available yet for this article.
November 2016: Journal of Thoracic Imaging
Vishnu Priya Bollampalli, Susanne Nylén, Antonio Gigliotti Rothfuchs
Dendritic cells (DCs) are important for initiating immune responses, in part through their ability to acquire and shuttle antigen to the draining lymph node (DLN). The mobilization of DCs to the DLN is complex and remains to be fully elucidated during infection. Herein described is the use of an innovative, simple assay that relies on the fluorochrome 5- and 6-carboxyfluorescein diacetate succinimidyl ester (CFSE) to track the migration of DCs during footpad infection with Mycobacterium bovis Bacille Calmette-Guérin (BCG) in C57BL/6 mice...
October 9, 2016: Journal of Visualized Experiments: JoVE
Sarah Thabet, Nada Souissi
The mycobacterial insertion sequence IS6110 proved crucial in deciphering tuberculosis (TB) transmission dynamics. This sequence was also shown to play an important role in the pathogenicity (transmission ability and/or virulence) of Mycobacterium tuberculosis, the main causative agent of TB in humans. In this study, we explored the usefulness of IS6110 and its potential as a phylogenetic/typing marker. We also analyzed the genetic polymorphism and evolutionary trends (selective pressure) of its transposase-encoding open reading frames (ORFs), A and B, using the maximum likelihood method...
October 20, 2016: Molecular Biology Reports
Jin Kyung Kim, Hye-Mi Lee, Ki-Sun Park, Dong-Min Shin, Tae Sung Kim, Yi Sak Kim, Hyun-Woo Suh, Soo Yeon Kim, In Soo Kim, Jin-Man Kim, Ji-Woong Son, Kyung Mok Sohn, Sung Soo Jung, Chaeuk Chung, Sang-Bae Han, Chul-Su Yang, Eun-Kyeong Jo
Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3'-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages...
October 20, 2016: Autophagy
Nathan J Hare, Ling Y Lee, Ian Loke, Warwick J Britton, Bernadette M Saunders, Morten Thaysen-Andersen
Tuberculosis (TB) remains a prevalent and lethal infectious disease. The glycobiology associated with Mycobacterium tuberculosis infection of front-line alveolar macrophages is still unresolved. Herein, we investigated the regulation of protein N-glycosylation in human macrophages and their secreted microparticles (MPs) used for intercellular communication upon M. tb infection. LC-MS/MS-based proteomics and glycomics were performed to monitor the regulation of glycosylation enzymes and receptors and the N-glycome in in vitro-differentiated macrophages and in isolated MPs upon M...
October 19, 2016: Journal of Proteome Research
Himanshu Pandey, Sarita Tripathi, Kanchan Srivastava, Dinesh K Tripathi, Mrigank Srivastava, Surya Kant, Kishore K Srivastava, Ashish Arora
BACKGROUND: We have characterized two immunogenic proteins, Rv1197 and Rv1198, of the Esx-5 system of the ESAT-6 family of Mycobacterium tuberculosis H37Rv. METHODS: The complex formation between Rv1197 and Rv1198 was characterized by biophysical techniques. The reactivity of serum from TB patients towards these proteins was characterized by ELISA. Lymphocyte proliferation and cytokine induction were followed in restimulated splenocytes from immunized mice by using MTT assay and CBA flowcytometry, respectively...
October 14, 2016: Biochimica et Biophysica Acta
Kenneth N Olivier, David E Griffith, Gina Eagle, John P McGinnis Ii, Liza Micioni, Keith Liu, Charles L Daley, Kevin L Winthrop, Stephen Ruoss, Doreen J Addrizzo-Harris, Patrick A Flume, Daniel Dorgan, Matthias Salathe, Barbara A Brown-Elliott, Renu Gupta, Richard J Wallace
Rationale Lengthy multi-drug, toxic, and low efficacy regimens limit management of pulmonary nontuberculous mycobacterial (PNTM) disease. Objective This phase 2 study investigated efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory PNTM (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease. Methods During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multi-drug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days...
October 17, 2016: American Journal of Respiratory and Critical Care Medicine
Liqin Wang, Miao Xu, Noel Southall, Wei Zheng, Shuishu Wang
Tuberculosis (TB) still kills over 1.5 million people per year despite available anti-TB drugs. The emergence of drug-resistant TB poses a major threat to public health and prompts for an urgent need for new and more effective drugs. The long duration needed to treat TB by the current TB drugs, which target the essential cellular activities, inevitably leads to the emergence of drug-resistance. PhoP of Mycobacterium tuberculosis (MTB), an essential virulence factor, is a novel target for drug development. Guided by the crystal structure of the PhoP-DNA complex, we designed and developed a robust high-throughput screening assay for identification of PhoP inhibitors that disrupt the PhoP-DNA binding...
October 10, 2016: Combinatorial Chemistry & High Throughput Screening
Susmita K Singh, Anna-Maria Andersson, Rada Ellegård, Cecilia S Lindestam Arlehamn, Alessandro Sette, Marie Larsson, Olle Stendahl, Robert Blomgran
HIV coinfection is the most prominent risk factor for progression of Mycobacterium tuberculosis (Mtb) infection into active tuberculosis (TB) disease. The mechanisms behind the increased transition from latent to active TB in coinfected individuals have not been well elucidated at the cellular level. We hypothesized that HIV infection contributes to Mtb pathogenesis by interfering with the dendritic cell (DC)-mediated immune control. Mtb-antigen processing and presentation are key events in the immune response against TB...
October 13, 2016: American Journal of Pathology
Kiran M Perkins, Adrian Lawsin, Nabeeh A Hasan, Michael Strong, Alison L Halpin, Rachael R Rodger, Heather Moulton-Meissner, Matthew B Crist, Suzanne Schwartz, Julia Marders, Charles L Daley, Max Salfinger, Joseph F Perz
In the spring of 2015, investigators in Switzerland reported a cluster of six patients with invasive infection with Mycobacterium chimaera, a species of nontuberculous mycobacterium ubiquitous in soil and water. The infected patients had undergone open-heart surgery that used contaminated heater-cooler devices during extracorporeal circulation (1). In July 2015, a Pennsylvania hospital also identified a cluster of invasive nontuberculous mycobacterial infections among open-heart surgery patients. Similar to the Swiss report, a field investigation by the Pennsylvania Department of Health, with assistance from CDC, used both epidemiologic and laboratory evidence to identify an association between invasive Mycobacterium avium complex, including M...
October 14, 2016: MMWR. Morbidity and Mortality Weekly Report
Hsiao-Ling Huang, Inna V Krieger, Maloy K Parai, Vijay B Gawandi, James C Sacchettini
Fragment screening and high-throughput screening are complementary approaches that go hand in hand with structural biology to explore the binding capabilities of an active site and to provide diversity for inhibitor design. We used fragment-based approaches on malate synthase (GlcB) from Mycobacterium tuberculosis and discovered several novel binding chemotypes. In addition, the crystal structures of GlcB in complex with these fragments indicated conformational changes in the active site hypothesized to represent states the enzyme assumes in the substrate-product exchange during catalysis...
October 13, 2016: Journal of Biological Chemistry
Juan Manuel Belardinelli, Amira Yazidi, Liang Yang, Lucien Fabre, Wei Li, Benoit Jacques, Shiva Kumar Angala, Isabelle Rouiller, Helen I Zgurskaya, Jurgen Sygusch, Mary Jackson
The MmpL family of proteins translocates complex (glyco)lipids and siderophores across the cell envelope of mycobacteria and closely related Corynebacteriaceae and plays important roles in the biogenesis of the outer membrane of these organisms. Despite their significance in the physiology and virulence of Mycobacterium tuberculosis, and from the perspective of developing novel antituberculosis agents, little is known about their structure and mechanism of translocation. In this study, the essential mycobacterial mycolic acid transporter, MmpL3, and its orthologue in Corynebacterium glutamicum, CmpL1, were investigated as prototypical MmpL proteins to gain insight into the transmembrane topology, tertiary and quaternary structures, and functional regions of this transporter family...
October 14, 2016: ACS Infectious Diseases
Ulziijargal Gurjav, Alexander C Outhred, Peter Jelfs, Nadine McCallum, Qinning Wang, Grant A Hill-Cawthorne, Ben J Marais, Vitali Sintchenko
Australia has a low tuberculosis incidence rate with most cases occurring among recent immigrants. Given suboptimal cluster resolution achieved with 24-locus mycobacterium interspersed repetitive unit (MIRU-24) genotyping, the added value of whole genome sequencing was explored. MIRU-24 profiles of all Mycobacterium tuberculosis culture-confirmed tuberculosis cases diagnosed between 2009 and 2013 in New South Wales (NSW), Australia, were examined and clusters identified. The relatedness of cases within the largest MIRU-24 clusters was assessed using whole genome sequencing and phylogenetic analyses...
2016: PloS One
Sabine Hofmann-Thiel, Nikolay Molodtsov, Uladzimir Antonenka, Harald Hoffmann
Abbott RealTime MTB (RT MTB) is a new automated nucleic acid amplification test for the detection of Mycobacterium tuberculosis complex (MTBC) in clinical specimens. In combination with RealTime MTB INH/RIF Resistance (RT MTB INH/RIF), which can be applied to RT MTB positive specimens as add-on assay, the tests also indicate genetic markers of resistance to isoniazid and rifampicin. We aimed to evaluate the diagnostic sensitivity and specificity of RT MTB using different types of respiratory and extra-pulmonary specimens and to compare performance characteristics directly with the FluoroType MTB assay...
October 12, 2016: Journal of Clinical Microbiology
M B Huante, S Gupta, V C Calderon, S J Koo, M Sinha, B A Luxon, N J Garg, J J Endsley
Pathogens frequently exploit or evade inflammasome activation in order to survive and proliferate. Alternatively, inadequate inflammasome activation by attenuated microorganisms or adjuvanted subunit vaccines may contribute to poor longevity of protection. To further understand these pathways, we determined the differential inflammasome transcriptome of human THP monocyte-derived macrophages in response to Mycobacterium bovis BCG, as compared to LPS or Trypanosoma cruzi. The results identify the highly specific innate recognition programs associated with inflammasome activation by human macrophages exposed to these microbial stimuli...
September 28, 2016: Tuberculosis
Yarrow Madrona, Christopher A Waddling, Paul R Ortiz de Montellano
DosS is a sensor in Mycobacterium tuberculosis that differentially responds to O2, NO, and CO, as well as to changes in the redox state of the prosthetic heme iron atom. The ferrous protein and its Fe(II)NO and Fe(II)CO complexes undergo autophosphorylation and subsequently transfer the phosphate group to DosR, a nuclear factor, to activate it. In contrast, autophosphorylation is negligible with the ferric protein and the Fe(II)O2 complex. To clarify the basis for this differential response to gases, we have determined the crystal structures of the NO and COcomplexes of the DosS GAF-A domain, which contains the heme to which the gases bind...
October 8, 2016: Archives of Biochemistry and Biophysics
Patricia J Simner, Gail L Woods, Nancy L Wengenack
The immunocompromised host is at increased risk of Mycobacterium tuberculosis complex and nontuberculous mycobacteria infection. Although Mycobacterium tuberculosis complex is a significant mycobacterial pathogen, nontuberculous mycobacteria causes substantial disease in those with suppressed immune responses. Mycobacterial infections can cause significant morbidity and mortality in this patient population, and rapid identification and susceptibility testing of the mycobacterial species is paramount to patient management and outcomes...
August 2016: Microbiology Spectrum
Maxime Barbier, Thierry Wirth
With the advent of next-generation sequencing technology, the genotyping of clinical Mycobacterium tuberculosis strains went through a major breakup that dramatically improved the field of molecular epidemiology but also revolutionized our deep understanding of the M. tuberculosis complex evolutionary history. The intricate paths of the pathogen and its human host are reflected by a common geographical origin in Africa and strong biogeographical associations that largely reflect the past migration waves out of Africa...
August 2016: Microbiology Spectrum
Ian M Orme, Diane J Ordway
This article describes the nature of the host response to Mycobacterium tuberculosis in the mouse and guinea pig models of infection. It describes the great wealth of information obtained from the mouse model, reflecting the general availability of immunological reagents, as well as genetic manipulations of the mouse strains themselves. This has led to a good understanding of the nature of the T-cell response to the infection, as well as an appreciation of the complexity of the response involving multiple cytokine- and chemokine-mediated systems...
August 2016: Microbiology Spectrum
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