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https://www.readbyqxmd.com/read/28224119/vesicular-stomatitis-virus-vectored-multi-antigen-tuberculosis-vaccine-limits-bacterial-proliferation-in-mice-following-a-single-intranasal-dose
#1
Ming Zhang, Chunsheng Dong, Sidong Xiong
Tuberculosis (TB) remains a serious health problem worldwide, and an urgent need exists to improve or replace the available vaccine, Mycobacterium bovis bacillus Calmette-Guérin (BCG). Most vaccination protocols adapt two or three doses to induce long-term lasting immunity. Our previous study showed that the naked DNA encoding the triple-antigen fusion TFP846 (Rv3615c-Mtb10.4-Rv2660c) induced robust T cellular immune responses accompanying four inoculations against mycobacteria infection. However, a number of compliance issues exist in some areas lacking the appropriate medical infrastructure with multiple administrations...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28221128/epidemiology-of-nontuberculous-mycobacterial-lung-disease-and-tuberculosis-hawaii-usa
#2
Jennifer Adjemian, Timothy B Frankland, Yihe G Daida, Jennifer R Honda, Kenneth N Olivier, Adrian Zelazny, Stacey Honda, D Rebecca Prevots
Previous studies found Hawaiians and Asian-Americans/Pacific Islanders to be independently at increased risk for nontuberculous mycobacterial pulmonary disease (NTMPD) and tuberculosis (TB). To better understand NTM infection and TB risk patterns in Hawaii, USA, we evaluated data on a cohort of patients in Hawaii for 2005-2013. Period prevalence of NTMPD was highest among Japanese, Chinese, and Vietnamese patients (>300/100,000 persons) and lowest among Native Hawaiians and Other Pacific Islanders (50/100,000)...
March 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28219077/radiopathological-features-and-identification-of-mycobacterial-infections-in-granulomatous-nodules-resected-from-the-lung
#3
Yumi Sakakibara, Yoshimi Suzuki, Toshihide Fujie, Takumi Akashi, Tadatsune Iida, Yasunari Miyazaki, Yoshinobu Eishi, Naohiko Inase
BACKGROUND: Pulmonary granulomas are sometimes resected because they resemble lung cancer and false-positive findings come through from positron emission tomography (PET) using 18fluorine-fluorodeoxyglucose (18F-FDG). Mycobacterial infection is a common cause of granulomas. OBJECTIVE: The purpose of this study was to evaluate the radiopathological features and the methods for identifying mycobacterial infections in granulomatous nodules resected from the lung. METHODS: Thirty-five solitary lesions resected because of suspected lung cancer were enrolled, including 22 nonfungal granulomatous lesions and 13 benign lesions as controls...
February 21, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28215633/tlr-4-mirna-32-5p-fstl1-signaling-regulates-mycobacterial-survival-and-inflammatory-responses-in-mycobacterium-tuberculosis-infected-macrophages
#4
Zhi-Min Zhang, Ai-Rong Zhang, Min Xu, Jun Lou, Wei-Qiang Qiu
Macrophages play a pivotal role in host immune response against mycobacterial infection, which is tightly modulated by multiple factors, including microRNAs. The purpose of the present study was to investigate the biological function and potential mechanism of miR-32-5p in human macrophages during Mycobacterium tuberculosis (M.tb) infection. The results demonstrated that miR-32-5p was robustly enhanced in THP-1 and U937 cells in response to M.tb infection. TLR-4 signaling was required for upregulation of miR-32-5p induced by M...
February 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28205597/the-influence-of-accd5-on-accd6-carboxyltransferase-essentiality-in-pathogenic-and-non-pathogenic-mycobacterium
#5
Jakub Pawelczyk, Albertus Viljoen, Laurent Kremer, Jaroslaw Dziadek
Malonyl-coenzyme A (CoA) is a crucial extender unit for the synthesis of mycolic and other fatty acids in mycobacteria, generated in a reaction catalyzed by acetyl-CoA carboxylase. We previously reported on the essentiality of accD6Mtb encoding the functional acetyl-CoA carboxylase subunit in Mycobacterium tuberculosis. Strikingly, the homologous gene in the fast-growing, non-pathogenic Mycobacterium smegmatis - (accD6Msm) appeared to be dispensable, and its deletion did not influence the cell lipid content...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28199374/a-novel-mycobacterial-in-vitro-infection-assay-identifies-differences-of-induced-macrophage-apoptosis-between-cd4-and-cd8-t-cells
#6
Vanesa Nkwouano, Sven Witkowski, Nidja Rehberg, Rainer Kalscheuer, Norman Nausch, Ertan Mayatepek, Marc Jacobsen
Macrophages are natural host cells for pathogenic mycobacteria, like Mycobacterium tuberculosis (M.tb). Immune surveillance by T cells and interaction with M.tb infected macrophages is crucial for protection against M.tb reactivation and development of active tuberculosis. Several factors play a role in the control of M.tb infection but reliable biomarkers remain elusive. One major obstacle is the absence of functional in vitro assays which allow concomitant determination of i) mycobacterial eradication; ii) cytotoxic effects on host macrophages; and iii) effector T-cell functions...
2017: PloS One
https://www.readbyqxmd.com/read/28198348/down-regulation-of-pe11-a-cell-wall-associated-esterase-enhances-the-biofilm-growth-of-mycobacterium-tuberculosis-and-reduces-cell-wall-virulence-lipid-levels
#7
Shivangi Rastogi, Amit Kumar Singh, Garima Pant, Kalyan Mitra, Koneni V Sashidhara, Manju Y Krishnan
PE11 (Rv1169c or LipX) is a cell wall associated esterase/lipase of Mycobacterium tuberculosis (Mtb). Evidences suggest that PE11 is expressed by Mtb both in vitro and in vivo. Previous studies have shown that PE11 leads to modification in cell wall lipid content and enhanced virulence when expressed in the non-pathogenic surrogate Mycobacterium smegmatis. Since cell wall lipids often play different roles in pathogenic and non-pathogenic mycobacteria, we investigated the role of PE11 in its host, Mtb. Mtb with lowered expression of PE11 (PE11 knock-down) displayed significant changes in colony morphology and cell wall lipid profile, confirming the role of PE11 in cell wall architecture...
January 2017: Microbiology
https://www.readbyqxmd.com/read/28196957/a-novel-small-molecule-inhibitor-of-the-mycobacterium-tuberculosis-demethylmenaquinone-methyltransferase-meng-is-bactericidal-to-both-growing-and-nutritionally-deprived-persister-cells
#8
Paridhi Sukheja, Pradeep Kumar, Nisha Mittal, Shao-Gang Li, Eric Singleton, Riccardo Russo, Alexander L Perryman, Riju Shrestha, Divya Awasthi, Seema Husain, Patricia Soteropoulos, Roman Brukh, Nancy Connell, Joel S Freundlich, David Alland
Active tuberculosis (TB) and latent Mycobacterium tuberculosis infection both require lengthy treatments to achieve durable cures. This problem has partly been attributable to the existence of nonreplicating M. tuberculosis "persisters" that are difficult to kill using conventional anti-TB treatments. Compounds that target the respiratory pathway have the potential to kill both replicating and persistent M. tuberculosis and shorten TB treatment, as this pathway is essential in both metabolic states. We developed a novel respiratory pathway-specific whole-cell screen to identify new respiration inhibitors...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28196707/antimicrobial-activity-of-rhodanine-3-acetic-acid-derivatives
#9
Martin Krátký, Jarmila Vinšová, Jiřina Stolaříková
Twenty-four 2-(4-oxo-2-thioxothiazolidin-3-yl)acetic acid (rhodanine-3-acetic acid)-based amides, esters and 5-arylalkylidene derivatives were synthesized, characterized and evaluated as potential antimicrobial agents against a panel of bacteria, mycobacteria and fungi. All of the derivatives were active against mycobacteria. N-(4-Chlorophenyl)-2-[5-(2-hydroxybenzylidene)-4-oxo-2-thioxothiazolidin-3-yl]acetamide demonstrated the highest activity against Mycobacterium tuberculosis with minimum inhibitory concentrations (MIC) of 8-16μM...
February 1, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28195652/identification-of-the-anti-mycobacterial-functional-properties-of-piperidinol-derivatives
#10
Collette S Guy, Esther Tichauer, Gemma L Kay, Daniel J Phillips, Trisha L Bailey, James Harrison, Christopher M Furze, Andrew D Millard, Matthew I Gibson, Mark J Pallen, Elizabeth Fullam
BACKGROUND AND PURPOSE: Tuberculosis (TB) remains a major global health threat and is now the leading cause of death from a single infectious agent worldwide. The current TB drug regimen is inadequate and new anti-tubercular agents are urgently required to be able to successfully combat the increasing prevalence of drug-resistant TB. The purpose of this study was to investigate a piperidinol compound derivative that is highly active against the Mycobacterium tuberculosis bacillus. EXPERIMENTAL APPROACH: The antibacterial properties of the piperidinol compound and its corresponding bis-Mannich base analogue were evaluated against Mycobacterium smegmatis and Gram-negative organisms...
February 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28194371/non-tuberculous-mycobacteria-in-south-african-wildlife-neglected-pathogens-and-potential-impediments-for-bovine-tuberculosis-diagnosis
#11
Nomakorinte Gcebe, Tiny M Hlokwe
Non-tuberculous mycobacteria (NTM) are not only emerging and opportunistic pathogens of both humans and animals, but from a veterinary point of view some species induce cross-reactive immune responses that hamper the diagnosis of bovine tuberculosis (bTB) in both livestock and wildlife. Little information is available about NTM species circulating in wildlife species of South Africa. In this study, we determined the diversity of NTM isolated from wildlife species from South Africa as well as Botswana. Thirty known NTM species and subspecies, as well as unidentified NTM, and NTM closely related to Mycobacterium goodii/Mycobacterium smegmatis were identified from 102 isolates cultured between the years 1998 and 2010, using a combination of molecular assays viz PCR and sequencing of different Mycobacterial house-keeping genes as well as single nucleotide polymorphism (SNP) analysis...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28193903/structural-analysis-of-mycobacterium-tuberculosis-homologues-of-the-eukaryotic-proteasome-assembly-chaperone-2-pac2
#12
Lin Bai, Jordan B Jastrab, Marta Isasa, Kuan Hu, Hongjun Yu, Steven P Gygi, K Heran Darwin, Huilin Li
A previous bioinformatics analysis identified the Mycobacterium tuberculosis (M. tuberculosis) proteins Rv2125 and Rv2714 as orthologs of the eukaryotic proteasome assembly chaperone 2 (PAC2). We set out to investigate whether Rv2125 or Rv2714 could function in proteasome assembly. We solved the crystal structure of Rv2125 at 3.0 Å resolution, which showed an overall fold similar to that of the PAC2 family proteins that include the archaeal PbaB and the yeast Pba1. However, Rv2125 and Rv2714 formed trimers, whereas PbaB forms tetramers and Pba1 dimerizes with Pba2...
February 13, 2017: Journal of Bacteriology
https://www.readbyqxmd.com/read/28185617/mycobacterium-kansasii
#13
James C Johnston, Leslie Chiang, Kevin Elwood
The incidence of Mycobacterium kansasii varies widely over time and by region, but this organism remains one of the most clinically relevant isolated species of nontuberculous mycobacteria. In contrast to other common nontuberculous mycobacteria, M. kansasii is infrequently isolated from natural water sources or soil. The major reservoir appears to be tap water. Infection is likely acquired through the aerosol route, with low infectivity in regions of endemicity. Human-to-human transmission is thought not to occur...
January 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28180188/imidazoles-induce-reactive-oxygen-species-in-mycobacterium-tuberculosis-which-is-not-associated-with-cell-death
#14
Heather A Howell Wescott, David M Roberts, Christian L Allebach, Rachel Kokoczka, Tanya Parish
Azoles are a class of antimicrobial drugs used clinically to treat yeast and fungal infections. Against pathogenic yeast and fungi, azoles act by inhibiting the activity of the cytochrome P450 Cyp51, which is involved in the synthesis of a critical component of the yeast and fungal cell membrane. Azoles have antibacterial activity, including against mycobacteria, but the basis for this activity is not well-understood. We demonstrated that imidazoles are bactericidal to Mycobacterium tuberculosis. A marked increase in reactive oxygen species (ROS) was observed within imidazole-treated M...
January 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28178706/coexistent-sarcoidosis-and-tuberculosis-a-case-report
#15
Cristiano Carbonelli, Ernesto Giuffreda, Antonio Palmiotti, Domenico Loizzi, Filippo Lococo, Elisiana Carpagnano, Donato Lacedonia, Francesco Sollitto, Maria Pia Foschino
Necrotizing granulomatous diseases of the lungs are usually dependent on a narrow range of differential diagnoses. Tuberculosis (TB) is responsible for the largest number of cases, while necrotizing sarcoidosis is generally considered a rare and easily distinguishable disease substantially based on histological features. However, this entity has become a viable diagnosis in the absence of mycobacteria isolation or when a remarkable clinical improvement cannot be achieved with the combination of anti-TB drugs at full dosage...
February 9, 2017: Respiration; International Review of Thoracic Diseases
https://www.readbyqxmd.com/read/28174310/the-antituberculosis-drug-ethambutol-selectively-blocks-apical-growth-in-cmn-group-bacteria
#16
Karin Schubert, Boris Sieger, Fabian Meyer, Giacomo Giacomelli, Kati Böhm, Angela Rieblinger, Laura Lindenthal, Nadja Sachs, Gerhard Wanner, Marc Bramkamp
: Members of the genus Mycobacterium are the most prevalent cause of infectious diseases. Mycobacteria have a complex cell envelope containing a peptidoglycan layer and an additional arabinogalactan polymer to which a mycolic acid bilayer is linked; this complex, multilayered cell wall composition (mAGP) is conserved among all CMN group bacteria. The arabinogalactan and mycolic acid synthesis pathways constitute effective drug targets for tuberculosis treatment. Ethambutol (EMB), a classical antituberculosis drug, inhibits the synthesis of the arabinose polymer...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28167550/acquisition-of-rifampin-resistance-in-pulmonary-tuberculosis
#17
Xavier A Kayigire, Sven O Friedrich, Lize van der Merwe, Andreas H Diacon
Mycobacterium tuberculosis with spontaneous mutations conferring resistance to rifampin (RIF) are exceedingly rare and fixed drug combinations typically prevent augmentation of resistance. Fourteen newly diagnosed tuberculosis patients were treated with RIF only for 14 days and bacterial loads including mutation frequencies were determined. A statistical model estimated that 1% of the remaining viable mycobacteria could be resistant after 30 days of monotherapy, indicating that pharmacodynamic variation could contribute to the acquisition of resistance against RIF...
February 6, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28165460/programmable-transcriptional-repression-in-mycobacteria-using-an-orthogonal-crispr-interference-platform
#18
Jeremy M Rock, Forrest F Hopkins, Alejandro Chavez, Marieme Diallo, Michael R Chase, Elias R Gerrick, Justin R Pritchard, George M Church, Eric J Rubin, Christopher M Sassetti, Dirk Schnappinger, Sarah M Fortune
The development of new drug regimens that allow rapid, sterilizing treatment of tuberculosis has been limited by the complexity and time required for genetic manipulations in Mycobacterium tuberculosis. CRISPR interference (CRISPRi) promises to be a robust, easily engineered and scalable platform for regulated gene silencing. However, in M. tuberculosis, the existing Streptococcus pyogenes Cas9-based CRISPRi system is of limited utility because of relatively poor knockdown efficiency and proteotoxicity. To address these limitations, we screened eleven diverse Cas9 orthologues and identified four that are broadly functional for targeted gene knockdown in mycobacteria...
February 6, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28159794/rifz-amed_0655-is-a-pathway-specific-regulator-for-rifamycin-biosynthesis-in-amycolatopsis-mediterranei
#19
Chen Li, Xinqiang Liu, Chao Lei, Han Yan, Zhihui Shao, Ying Wang, Guoping Zhao, Jin Wang, Xiaoming Ding
: Rifamycin and its derivatives are particularly effective against the pathogenic mycobacteria Mycobacterium tuberculosis and Mycobacterium leprae Although the biosynthetic pathway of rifamycin has been extensively studied in Amycolatopsis mediterranei, little is known about the regulation in rifamycin biosynthesis. Here, an in vivo transposon system was employed to identify genes involved in the regulation of rifamycin production in A. mediterranei U32. Totally, nine rifamycin-defecient mutants were isolated, among which three mutants had the transposon inserted in AMED_0655 (namely rifZ, encoding a LuxR_family regulator)...
February 3, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28159576/humoral-immune-profiling-of-mycobacterial-antigen-recognition-in-sarcoidosis-and-l%C3%A3-fgren-s-syndrome-using-high-content-peptide-microarrays
#20
REVIEW
Giovanni Ferrara, Davide Valentini, Martin Rao, Jan Wahlström, Johan Grunewald, Lars-Olof Larsson, Susanna Brighenti, Ernest Dodoo, Alimuddin Zumla, Markus Maeurer
INTRODUCTION: Sarcoidosis is considered an idiopathic granulomatous disease, although similar immunological and clinical features with tuberculosis (TB) suggest mycobacterial involvement in its pathogenesis. High-content peptide microarrays (HCPM) may help to decipher mycobacteria-specific antibody reactivity in sarcoidosis. METHODS: Serum samples from patients with sarcoidosis, Löfgren's syndrome, and TB, as well as from healthy individuals (12/group), were tested on HCPM containing 5964 individual peptides spanning 154 Mycobacterium tuberculosis proteins displayed as 15-amino acid stretches...
January 31, 2017: International Journal of Infectious Diseases: IJID
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