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Pathogenesis AND Tuberculosis

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https://www.readbyqxmd.com/read/28513416/the-role-of-esx-1-in-mycobacterium-tuberculosis-pathogenesis
#1
Ka-Wing Wong
In this article, we have described several cellular pathological effects caused by the Mycobacterium tuberculosis ESX-1. The effects include induction of necrosis, NOD2 signaling, type I interferon production, and autophagy. We then attempted to suggest that these pathological effects are mediated by the cytosolic access of M. tuberculosis-derived materials as a result of the phagosome-disrupting activity of the major ESX-1 substrate ESAT-6. Such activity of ESAT-6 is most likely due to its pore-forming activity at the membrane...
May 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28507063/the-mycobacterium-tuberculosis-mmpl11-cell-wall-lipid-transporter-is-important-for-biofilm-formation-intracellular-growth-and-non-replicating-persistence
#2
Catherine C Wright, Fong Fu Hsu, Eusondia Arnett, Jennifer L Dunaj, Patrick M Davidson, Sophia A Pacheco, Melanie J Harriff, David M Lewinsohn, Larry S Schlesinger, Georgiana E Purdy
The mycobacterial cell wall is crucial to the host-pathogen interface since it provides a barrier against antibiotics and the host immune response. In addition, cell wall lipids are mycobacterial virulence factors. The mycobacterial membrane protein large (MmpL) proteins are cell wall lipid transporters that are important for basic mycobacterial physiology and M. tuberculosis pathogenesis. MmpL3 and MmpL11 are conserved across pathogenic and nonpathogenic mycobacteria, consistent with an important role in the basic physiology of the bacterium...
May 15, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28500851/calreticulin-modulates-the-intracellular-survival-of-mycobacteria-by-regulating-er-stress-mediated-apoptosis
#3
Sung Hee Jo, Ji-Ae Choi, Yun-Ji Lim, Junghwan Lee, Soo-Na Cho, Sung-Man Oh, Dam Go, Seon-Hwa Kim, Chang-Hwa Song
Endoplasmic reticulum (ER)-stress-mediated apoptosis is a host defense mechanism against Mycobacterium tuberculosis (Mtb) infection. Calreticulin (CRT) is the major calcium-binding chaperone protein. Previous reports have suggested a close relationship between the cell-surface expression of CRT and apoptosis. In this study, the role of CRT during Mtb infection was examined. The results showed that Mtb infection induces CRT production by macrophages and that CRT levels are correlated with the degree of apoptotic cell death...
April 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28495854/role-of-apoptosis-and-autophagy-in-tuberculosis
#4
Adam Lam, Rohan Prabhu, Christine M Gross, Lee Ann Riesenberg, Vinodkumar Singh, Saurabh Aggarwal
Tuberculosis (TB) is one of the oldest known human diseases and is transmitted by the bacteria, Mycobacterium tuberculosis (Mtb). TB has a rich history with evidence of TB infections dating back to 5,800 B.C. TB is unique in its ability to remain latent in an individual for decades, with the possibility of later reactivation, causing widespread systemic symptoms. Currently, it is estimated that more than one-third of the world's population (about 2 billion people) are infected with Mtb. Prolonged periods of therapy and complexity of treatment regimens, especially in active infection, have led to poor compliance in patients being treated for TB...
May 11, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28484686/impact-of-pe_pgrs33-gene-polymorphisms-on-mycobacterium-tuberculosis-infection-and-pathogenesis
#5
Serena Camassa, Ivana Palucci, Raffaella Iantomasi, Tiziana Cubeddu, Mariachiara Minerva, Flavio De Maio, Samuel Jouny, Elisa Petruccioli, Delia Goletti, Francesco Ria, Michela Sali, Maurizio Sanguinetti, Riccardo Manganelli, Stefano Rocca, Priscille Brodin, Giovanni Delogu
PE_PGRS33 is a surface-exposed protein of Mycobacterium tuberculosis (Mtb) which exerts its role in macrophages entry and immunomodulation. In this study, we aimed to investigate the polymorphisms in the pe_pgrs33 gene of Mtb clinical isolates and evaluate their impact on protein functions. We sequenced pe_pgrs33 in a collection of 135 clinical strains, genotyped by 15-loci MIRU-VNTR and spoligotyping and belonging to the Mtb complex (MTBC). Overall, an association between pe_pgrs33 alleles and MTBC genotypes was observed and a dN/dS ratio of 0...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28482027/cmr-is-a-redox-responsive-regulator-of-dosr-that-contributes-to-m-tuberculosis-virulence
#6
Laura J Smith, Aleksandra Bochkareva, Matthew D Rolfe, Debbie M Hunt, Christina Kahramanoglou, Yvonne Braun, Angela Rodgers, Alix Blockley, Stephen Coade, Kathryn E A Lougheed, Nor Azian Hafneh, Sarah M Glenn, Jason C Crack, Nick E Le Brun, José W Saldanha, Vadim Makarov, Irene Nobeli, Kristine Arnvig, Galina V Mukamolova, Roger S Buxton, Jeffrey Green
Mycobacterium tuberculosis (MTb) is the causative agent of pulmonary tuberculosis (TB). MTb colonizes the human lung, often entering a non-replicating state before progressing to life-threatening active infections. Transcriptional reprogramming is essential for TB pathogenesis. In vitro, Cmr (a member of the CRP/FNR super-family of transcription regulators) bound at a single DNA site to act as a dual regulator of cmr transcription and an activator of the divergent rv1676 gene. Transcriptional profiling and DNA-binding assays suggested that Cmr directly represses dosR expression...
May 8, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28466489/characterization-of-mycobacterium-marinum-infections-in-zebrafish-wounds-and-sinus-tracts
#7
Ling Chen, Zhen Liu, Yingjun Su, Di Wang, Bin Yin, Bin Shu, Jishen Zhang, Xiaoyan Zhu, Chiyu Jia
The impaired healing of Mycobacterium tuberculosis-infected wounds is a clinical challenge, and the mechanisms involved are still not clear. The zebrafish model of Mycobacterium marinum infection has provided surprising insights into the pathogenesis of tuberculosis in humans. Similarly, the major principles and phases of cutaneous wound healing are conserved among adult mammals and adult zebrafish. Here, we injected Mycobacterium marinum into the dorsal muscles of adult zebrafish and observed the development of chronic wound pathology...
May 2, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28464471/chemical-activation-of-adenylyl-cyclase-rv1625c-inhibits-growth-of-mycobacterium-tuberculosis-on-cholesterol-and-modulates-intramacrophage-signaling
#8
Richard M Johnson, Guangchun Bai, Christopher M DeMott, Nilesh K Banavali, Christine R Montague, Caroline Moon, Alexander Shekhtman, Brian VanderVen, Kathleen A McDonough
Mycobacterium tuberculosis (Mtb) uses a complex 3'-5'-cyclic AMP (cAMP) signaling network to sense and respond to changing environments encountered during infection, so perturbation of cAMP signaling might be leveraged to disrupt Mtb pathogenesis. However, understanding of cAMP signaling pathways is hindered by the presence of at least 15 distinct adenylyl cyclases (ACs). Recently, the small molecule V-58 was shown to inhibit Mtb replication within macrophages and stimulate cAMP production in Mtb. Here we determined that V-58 rapidly and directly activates Mtb AC Rv1625c to produce high levels of cAMP regardless of the bacterial environment or growth medium...
May 2, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28443685/lymphatic-changes-in-respiratory-diseases-more-than-just-remodeling-of-the-lung
#9
Benjamin Stump, Ye Cui, Pranav Kidambi, Anthony M Lamattina, Souheil El-Chemaly
Advances in our ability to identify lymphatic endothelial cells and differentiate them from blood endothelial cells have led to important progress in the study of lymphatic biology. Over the past decade, pre-clinical and clinical studies have shown that there are changes to the lymphatic vasculature in nearly all lung diseases. Efforts to understand the contribution of lymphatics and their growth factors to disease initiation, progression and resolution have led to seminal findings establishing critical roles for lymphatics in lung biology spanning from the first breath after birth to asthma, tuberculosis, and lung transplantation...
April 26, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28440335/mycobacterium-tuberculosis-pe_pgrs41-enhances-the-intracellular-survival-of-m-smegmatis-within-macrophages-via-blocking-innate-immunity-and-inhibition-of-host-defense
#10
Wanyan Deng, Quanxin Long, Jie Zeng, Ping Li, Wenmin Yang, Xinchun Chen, Jianping Xie
The success of Mycobacterium tuberculosis (M. tuberculosis) as a pathogen is largely contributes to its ability to manipulate the host immune responses. The genome of M. tuberculosis encodes multiple immune-modulatory proteins, including several members of the multi-genic PE_PPE family. Despite of intense research, the roles of PE_PGRS proteins in mycobacterial pathogenesis remain elusive. The function of M. tuberculosis PE_PGRS41, characterized by an extended and unique C-terminal domain, was studied. Expression of PE_PGRS41 in Mycobacterium smegmatis, a non-pathogenic species intrinsically deficient of PE_PGRS, severely impaired the resistance of the recombinant to multiple stresses via altering the cell wall integrity...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28424682/interactions-between-type-1-interferons-and-the-th17-response-in-tuberculosis-lessons-learned-from-autoimmune-diseases
#11
REVIEW
Bas C Mourik, Erik Lubberts, Jurriaan E M de Steenwinkel, Tom H M Ottenhoff, Pieter J M Leenen
The classical paradigm of tuberculosis (TB) immunity, with a central protective role for Th1 responses and IFN-γ-stimulated cellular responses, has been challenged by unsatisfactory results of vaccine strategies aimed at enhancing Th1 immunity. Moreover, preclinical TB models have shown that increasing IFN-γ responses in the lungs is more damaging to the host than to the pathogen. Type 1 interferon signaling and altered Th17 responses have also been associated with active TB, but their functional roles in TB pathogenesis remain to be established...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28412202/the-immunosuppressive-effects-of-a-novel-recombinant-lipq-rv2485c-protein-of-mycobacterium-tuberculosis-on-human-macrophage-cell-lines
#12
Anjani Kumar, Manisha, Gurkamaljit Kaur Sangha, Anju Shrivastava, Jagdeep Kaur
Mycobacterium tuberculosis (MTB), an intracellular pathogen, still represents a major global health challenge. A number of mycobacterial macromolecules have been shown to target biological processes within host macrophages; however, the exact mechanism for the majority of these host pathogen interactions is still poorly understood. Moreover, the lipid metabolic pathway is one of the most important physiologic pathways that plays a vital role in the survival and infection of Mycobacterium tuberculosis. In present study, we investigated the effect of rLipQ from Mycobacterium tuberculosis H37Rv on macrophage functions in vitro...
April 12, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28403225/association-of-vitamin-d-deficiency-season-of-the-year-and-latent-tuberculosis-infection-among-household-contacts
#13
María Elvira Balcells, Patricia García, Camila Tiznado, Luis Villarroel, Natalia Scioscia, Camila Carvajal, Francesca Zegna-Ratá, Mariluz Hernández, Paulina Meza, Luis F González, Carlos Peña, Rodrigo Naves
OBJECTIVES: Vitamin D (VD) enhances the immune response against Mycobacterium tuberculosis in vitro, and VD deficiency has been described in patients with active tuberculosis (TB). However, the role of hypovitaminosis D in the pathogenesis of early TB infection acquisition is unclear. We aimed to evaluate the association of VD deficiency, season of the year, and latent TB infection in household contacts (HHC), given that this is a potentially modifiable condition often related to nutritional deficiencies and lack of sun exposure...
2017: PloS One
https://www.readbyqxmd.com/read/28401933/bcl-xl-mediates-ripk3-dependent-necrosis-in-m-tuberculosis-infected-macrophages
#14
X Zhao, N Khan, H Gan, F Tzelepis, T Nishimura, S-Y Park, M Divangahi, H G Remold
Virulent Mycobacterium tuberculosis (Mtb) triggers necrosis in host Mϕ, which is essential for successful pathogenesis in tuberculosis. Here we demonstrate that necrosis of Mtb-infected Mϕ is dependent on the action of the cytosolic Receptor Interacting Protein Kinase 3 (RIPK3) and the mitochondrial Bcl-2 family member protein B-cell lymphoma-extra large (Bcl-xL). RIPK3-deficient Mϕ are able to better control bacterial growth in vitro and in vivo. Mechanistically, cytosolic RIPK3 translocates to the mitochondria where it promotes necrosis and blocks caspase 8-activation and apoptosis via Bcl-xL...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28391322/evolutionary-thrift-mycobacteria-repurpose-plasmid-diversity-during-adaptation-of-type-vii-secretion-systems
#15
Tatum D Mortimer, Alexandra M Weber, Caitlin S Pepperell
Mycobacteria have a distinct secretion system, termed type VII (T7SS), which is encoded by paralogous chromosomal loci (ESX) and associated with pathogenesis, conjugation, and metal homeostasis. Evolution of paralogous gene families is of interest because duplication is an important mechanism by which novel genes evolve, but there are potential conflicts between adaptive forces that stabilize duplications and those that enable evolution of new functions. Our objective was to delineate the adaptive forces underlying diversification of T7SS...
March 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28387180/mycobacterium-marinum
#16
Alexandra Aubry, Faiza Mougari, Florence Reibel, Emmanuelle Cambau
Mycobacterium marinum is a well-known pathogenic mycobacterium for skin and soft tissue infections and is associated with fishes and water. Among nontuberculous mycobacteria (NTM), it is the leading cause of extrarespiratory human infections worldwide. In addition, there is a specific scientific interest in M. marinum because of its genetic relatedness to Mycobacterium tuberculosis and because experimental infection of M. marinum in fishes mimics tuberculosis pathogenesis. Microbiological characteristics include the fact that it grows in 7 to 14 days with photochromogenic colonies and is difficult to differentiate from Mycobacterium ulcerans and other mycolactone-producing NTM on a molecular basis...
April 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28387178/the-sec-pathways-and-exportomes-of-mycobacterium-tuberculosis
#17
Brittany K Miller, Katelyn E Zulauf, Miriam Braunstein
All bacteria utilize pathways to export proteins from the cytoplasm to the bacterial cell envelope or extracellular space. Many exported proteins function in essential physiological processes or in virulence. Consequently, the responsible protein export pathways are commonly essential and/or are important for pathogenesis. The general Sec protein export pathway is conserved and essential in all bacteria, and it is responsible for most protein export. The energy for Sec export is provided by the SecA ATPase...
April 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28384354/sustained-elevated-levels-of-c-reactive-protein-and-ferritin-in-pulmonary-tuberculosis-patients-remaining-culture-positive-upon-treatment-initiation
#18
Pryscila Miranda, Leonardo Gil-Santana, Marina G Oliveira, Eliene D D Mesquita, Elisangela Silva, Anneloek Rauwerdink, Frank Cobelens, Martha M Oliveira, Bruno B Andrade, Afrânio Kritski
BACKGROUND: Clinical trials that evaluate new anti-tubercular drugs and treatment regimens take years to complete due to the slow clearance of Mycobacterium tuberculosis infection and the lack of early biomarkers that predict treatment outcomes. Host Inflammation markers have been associated with tuberculosis (TB) pathogenesis. In the present study, we tested if circulating levels of C-reactive protein (CRP) and ferritin reflect mycobacterial loads and inflammation in pulmonary TB (PTB) patients undergoing anti-tuberculous therapy (ATT)...
2017: PloS One
https://www.readbyqxmd.com/read/28384290/mait-cells-are-reduced-in-frequency-and-functionally-impaired-in-human-t-lymphotropic-virus-type-1-infection-potential-clinical-implications
#19
Dominic Paquin-Proulx, Benjamin C Greenspun, Emanuela A S Costa, Aluisio C Segurado, Esper G Kallas, Douglas F Nixon, Fabio E Leal
HTLV-1 infection is associated with several inflammatory disorders, including the neurodegenerative condition HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is unclear why a minority of infected subjects develop HAM/TSP. The cellular immune response has been implicated in the development of inflammatory alterations in these patients; however the pathogenic mechanisms for disease progression remain unclear. Furthermore, HTLV-1-infected individuals have an increase incidence of Mycobacterium tuberculosis (Mtb) infection, suggesting that immunological defect are associated with HTLV-1 infection...
2017: PloS One
https://www.readbyqxmd.com/read/28374704/-a-case-report-of-central-pontine-and-extrapontine-myelinolysis-in-the-combination-with-spinal-cord-damage-in-a-patient-with-tuberculosis-in-the-lung
#20
A A Savin, S A Trukhanov, Yu R Zyuzya, I A Sokolina, E M Malysheva, D V Bogomolov, E B Savina, G V Khodyachaya, L A Savin, N N Matrokhin, A V Bugun
A case report of central pontine and extrapontine myelinolysis in the combination with spinal cord damage is presented. The authors analyze literature data on this problem and discuss the pathogenesis and diagnostic issues of myelinolysis.
2017: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
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