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Tuberculosis

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https://www.readbyqxmd.com/read/30205975/the-eu-approved-antimalarial-pyronaridine-shows-antitubercular-activity-and-synergy-with-rifampicin-targeting-rna-polymerase
#1
Giorgia Mori, Beatrice Silvia Orena, Clara Franch, Lesley A Mitchenall, Adwait Anand Godbole, Liliana Rodrigues, Clara Aguilar-Pérez, Júlia Zemanová, Stanislav Huszár, Martin Forbak, Thomas R Lane, Mohamad Sabbah, Nathalie Deboosere, Rosangela Frita, Alexandre Vandeputte, Eik Hoffmann, Riccardo Russo, Nancy Connell, Courtney Veilleux, Rajiv K Jha, Pradeep Kumar, Joel S Freundlich, Priscille Brodin, Jose Antonio Aínsa, Valakunja Nagaraja, Anthony Maxwell, Katarína Mikušová, Maria Rosalia Pasca, Sean Ekins
The search for compounds with biological activity for many diseases is turning increasingly to drug repurposing. In this study, we have focused on the European Union-approved antimalarial pyronaridine which was found to have in vitro activity against Mycobacterium tuberculosis (MIC 5 μg/mL). In macromolecular synthesis assays, pyronaridine resulted in a severe decrease in incorporation of 14 C-uracil and 14 C-leucine similar to the effect of rifampicin, a known inhibitor of M. tuberculosis RNA polymerase...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205974/genetic-diversity-of-mycobacterium-tuberculosis-complex-isolates-circulating-in-an-area-with-high-tuberculosis-incidence-using-24-locus-miru-vntr-method
#2
Noormohamad Mansoori, Mehdi Yaseri, Farzam Vaziri, Masoumeh Douraghi
We aimed to determine the genetic diversity, phylogenetic relationship and transmission dynamics of Mycobacterium tuberculosis complex (MTBC) genotypes in an area with high tuberculosis (TB) incidence. A set of 164 MTBC isolates from new TB patients of Golestan province, Iran, were subjected to genotyping using the standard 24-locus MIRU-VNTR method. Recent TB transmission was evaluated and phylogenetic relationships were analysed by minimum spanning tree and cluster-graph methods. Among the 164 isolates, 132 distinct patterns were detected...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205973/in-silico-designing-of-domain-b-selective-gyrase-inhibitors-for-effective-treatment-of-resistant-tuberculosis
#3
Aanchal Kashyap, Pankaj Kumar Singh, Om Silakari
One of the major mechanisms followed by the therapeutic agents to target the causative organism of TB, Mycobacterium tuberculosis, involves disruption of its DNA replication cycle. The process of replication involves two steps, i.e., breakage and reunion of DNA at gyrase A (GyrA) domain and ATP hydrolysis at gyrase B (GyrB) domain, both occur simultaneously. Current therapy for multi-drug resistant TB (MDR-TB) involves FDA approved, fluoroquinolone-based antibiotics, which act by targeting replication process at GyrA domain...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205972/centrifugation-and-decontamination-procedures-selectively-impair-recovery-of-important-populations-in-mycobacterium-smegmatis
#4
John A Kennedy, Vincent O Baron, Robert J H Hammond, Derek J Sloan, Stephen H Gillespie
Diagnosis and treatment monitoring of patients with tuberculosis (TB) requires detection of all viable mycobacteria in clinical samples. Quantitation of Mycobacterium tuberculosis (Mtb) in sputum is commonly performed by culture after sample decontamination to prevent overgrowth by contaminant organisms. Exponentially growing cultures have cells that predominately lack non-polar lipid bodies whereas stationary cultures have a predominance of cells with non-polar lipid bodies. This may reflect rapidly growing 'active' and non-replicating 'persister' sub-populations respectively in sputum from TB patients...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205971/a-katg-s315t-or-an-ahpc-promoter-mutation-mediate-mycobacterium-tuberculosis-resistance-to-2-thiophen-carboxylic-acid-hydrazide-an-inhibitor-resembling-the-anti-tubercular-drugs-isoniazid-and-ethionamide
#5
Jorgelina J Franceschelli, Juan M Belardinelli, Ping Tong, Brendan Loftus, Alejandro Recio-Balsells, Guillermo R Labadié, Stephen V Gordon, Hector R Morbidoni
Clinical isolates of Mycobacterium tuberculosis and Mycobacterium bovis are differentially susceptible to 2-Thiophen Hydrazide (TCH); however its mechanism of action or the reasons for that difference are unknown. We report herein that under our experimental conditions, TCH inhibits M. tuberculosis in solid but not in liquid medium, and that in spite of resembling Isoniazid and Ethionamide, it does not affect mycolic acid synthesis. To understand the mechanisms of action of TCH we isolated M. tuberculosis TCH resistant mutants which fell into two groups; one resistant to TCH and Isoniazid but not to Ethionamide or Triclosan, and the other resistant only to TCH with no, or marginal, cross resistance to Isoniazid...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205970/novel-mpra-binding-motifs-in-the-phop-regulatory-region-in-mycobacterium-tuberculosis
#6
Peipei Zhang, Jiafang Fu, Gongli Zong, Meng Liu, Xiuhua Pang, Guangxiang Cao
MprAB and PhoPR are important two-component systems (TCSs) in Mycobacterium tuberculosis, and both regulate EspR, a key regulator of the ESX-1 secretion system. Although previous studies suggest that the response regulator PhoP does not directly regulate mprA, the interplay between MprAB and PhoPR remains unclear. In this study, we found that the response regulator MprA can bind to the phoP promoter. Four repeat motifs, D1-D4, constituting two predicted binding sites, were located in the region protected by MprA in DNA footprinting...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205969/application-of-multiplexed-ion-mobility-spectrometry-towards-the-identification-of-host-protein-signatures-of-treatment-effect-in-pulmonary-tuberculosis
#7
Komal Kedia, Jason P Wendler, Erin S Baker, Kristin E Burnum-Johnson, Leah G Jarsberg, Kelly G Stratton, Aaron T Wright, Paul D Piehowski, Marina A Gritsenko, David M Lewinsohn, George B Sigal, Marc H Weiner, Richard D Smith, Jon M Jacobs, Payam Nahid
RATIONALE: The monitoring of TB treatments in clinical practice and clinical trials relies on traditional sputum-based culture status indicators at specific time points. Accurate, predictive, blood-based protein markers would provide a simpler and more informative view of patient health and response to treatment. OBJECTIVE: We utilized sensitive, high throughput multiplexed ion mobility-mass spectrometry (IM-MS) to characterize the serum proteome of TB patients at the start of and at 8 weeks of rifamycin-based treatment...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205968/human-tuberculosis-brain-promotes-neuronal-apoptosis-but-not-in-astrocytes-with-high-expression-of-vascular-endothelial-growth-factor
#8
Fatihah N Othman, Sangu Muthuraju, Siti Suraiya M Noor, Sarimah Abdullah, Abdul Aziz Mohd Yusoff, John Tharakan, Shalini Bhaskar, Mohd Shah Mahmood, Fauziah Kassim, Hanip Rafia, Mohd Saffari Mohd Haspani, Azmi Alias, Rogelio H Pando, Jafri M Abdullah, Hasnan Jaafar
The present study aimed to investigate the involvement of the angiogenic marker vascular endothelia growth factor (VEGF) and apoptotic markers of Bcl-2 and Bax in the neurons and astrocytes in the brain infected by Mycobacterium tuberculosis. The immunohistochemistry staining was performed to analyze the expression of the VEGF, Bcl-2 and Bax in the astrocytes and neurons. The expression of VEGF was high in neurons and astrocytes in both the infected brain and control tissues with no difference of angiogenic activity (p = 0...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205967/imb-sd62-a-triazolothiadiazoles-derivative-with-promising-action-against-tuberculosis
#9
Qi Deng, Jianzhou Meng, Yishuang Liu, Yan Guan, Chunling Xiao
One lead 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole was identified as an inhibitor of shikimate dehydrogenase with antitubercular activity. Following up this compound, we optimized the lead through systematic modification of the 3 and 6 positions. The antitubercular activities in vitro, shikimate dehydrogenase inhibitory activities and cytotoxicity of derivatives were determined. We found IMB-SD62 with lower cytotoxicity and better activity. Thus, we studied the in vivo efficacy of IMB-SD62 against Mycobacterium tuberculosis and pharmacokinetics of IMB-SD62...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205966/generation-and-application-of-dna-aptamers-against-hspx-for-accurate-diagnosis-of-tuberculous-meningitis
#10
Abhijeet Dhiman, Sagarika Haldar, Subodh Kumar Mishra, Neera Sharma, Anjali Bansal, Yusra Ahmad, Amit Kumar, Tarun Kumar Sharma, Jaya Sivaswami Tyagi
Tuberculous meningitis (TBM) is the most severe manifestation of tuberculosis and its diagnosis remains a challenge even today due to the lack of an adequate test. HspX antigen of Mycobacterium tuberculosis was previously established as a reliable diagnostic biomarker for TBM in an ELISA test format using anti-HspX polyclonal antibodies. Towards overcoming the limitations of batch-to-batch variation and challenges of scalability in antibody generation, we utilized Systematic Evolution of Ligands by EXponential enrichment (SELEX) to develop high affinity DNA aptamers against HspX as an alternative diagnostic reagent...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205965/a-genotypic-and-spatial-epidemiologic-analysis-of-massachusetts-mycobacterium-tuberculosis-cases-from-2012-to-2015
#11
T Vindenes, M R Jordan, A Tibbs, T J Stopka, D Johnson, J Cochran
BACKGROUND: Massachusetts had a rate of 2.8 cases of tuberculosis (TB) per 100,000 individuals in 2015. Although TB in Massachusetts is on the decline, the case rate remains far above the 2020 National TB Target of 1.4 per 100,000. To reduce the TB case rate in Massachusetts, it is necessary to understand the local epidemiology and transmission risks. METHODS: We used an existing TB case database of Massachusetts TB cases in the time frame from 2012 to 2015, which links de-identified patient demographic information with TB genotypes obtained from the United States Centers for Disease Control and Prevention's (CDC) TB Genotyping Information Management System database...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205964/diagnostic-evaluation-of-an-in-house-developed-single-tube-duplex-nested-is6110-real-time-pcr-assay-for-rapid-pulmonary-tuberculosis-diagnosis
#12
Kenneth Siu-Sing Leung, Gilman Kit-Hang Siu, Kingsley King-Gee Tam, Pak-Leung Ho, Samson Sai-Yin Wong, Eunice Ka-Chun Leung, Shi Hui Yu, Oliver Chiu-Kit Ma, Wing-Cheong Yam
OBJECTIVE: To perform a prospective evaluation on the diagnostic performance of an in-house developed, duplex nested IS6110 real-time Polymerase-Chain-Reaction (PCR) assay (IS6110-qPCR assay) for rapid pulmonary TB diagnosis. METHODS: A total of 503 sputum specimens were prospectively collected from July 2016 to November 2016. Diagnostic accuracy and optimal cut-off Cycle-threshold (Ct) value for IS6110-qPCR assay was determined by Receiver Operating Characteristic (ROC) curve...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205963/diagnostic-performance-of-gm-csf-and-il-2-in-response-to-long-term-specific-antigen-cell-stimulation-in-patients-with-active-and-latent-tuberculosis-infection
#13
María Elvira Balcells, Cinthya Ruiz-Tagle, Camila Tiznado, Patricia García, Rodrigo Naves
BACKGROUND: A simple blood test for detecting active tuberculosis (TB) could be key to this epidemic containment, given that a large proportion of patients are unable to produce sputum for testing. Currently available interferon-γ release assays (IGRAs) are inadequate to diagnose active TB, with reported pooled sensitivity and specificity both under 81%. OBJECTIVE: To explore whether cytokines/chemokines other than interferon-γ in response to long-term cell stimulation could improve the ability to distinguish between different TB infection status...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205962/single-nucleotide-polymorphisms-of-beijing-lineage-mycobacterium-tuberculosis-toxin-antitoxin-system-genes-their-role-in-the-changes-of-protein-activity-and-evolution
#14
M V Zaychikova, N E Mikheecheva, Y O Belay, M G Alekseeva, A V Melerzanov, V N Danilenko
The article investigates SNP in genes of toxin-antitoxin systems type II in Mycobacterium tuberculosis Beijing lineage strains and their possible role in the development and formation of new sublineages. We established the catalog of SNPs in 142 TA systems genes in 1349 sequenced genomes of the M. tuberculosis Beijing lineage. Based on the catalog, 15 new sublineages were identified as part of Beijing lineages by non-synonymous SNP in 21 genes of TA systems. We discovered three toxin genes with mutations specific for epidemiologically dangerous sublineages Beijing-modern (vapC37 A46G, vapC38 T143C) and Beijing-B0/W148 (vapC12 A95G)...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30205961/mycobacterium-tuberculosis-cording-in-alveolar-macrophages-of-patients-with-pulmonary-tuberculosis-is-likely-associated-with-increased-mycobacterial-virulence
#15
Elena G Ufimtseva, Natalya I Eremeeva, Ekaterina M Petrunina, Tatiana V Umpeleva, Sergey I Bayborodin, Diana V Vakhrusheva, Sergey N Skornyakov
Mycobacterium tuberculosis (Mtb) is an infectious agent that causes tuberculosis (TB) in humans. A study of the volume of Mtb population and the detection of Mtb virulence in the lungs of patients with pulmonary TB are of great importance for understanding the infectious process and the outcome of the disease. We analyzed the functional state of Mtb and their number in alveolar macrophages obtained from the resected lungs of patients with TB in ex vivo culture and determined that the number of Mtb, referred mainly to the Beijing genotype family (A0 and B0/W148 clusters), were significantly different in cells between different patients...
September 2018: Tuberculosis
https://www.readbyqxmd.com/read/30029922/screening-for-active-pulmonary-tuberculosis-development-and-applicability-of-artificial-neural-network-models
#16
João Baptista de Oliveira E Souza Filho, Mauro Sanchez, José Manoel de Seixas, Carmen Maidantchik, Rafael Galliez, Adriana da Silva Rezende Moreira, Paulo Albuquerque da Costa, Martha Maria Oliveira, Anthony David Harries, Afrânio Lineu Kritski
Tuberculosis (TB) remains a significant public health challenge, motivated by the diversity of healthcare epidemiological settings, as other factors. Cost-effective screening has substantial importance for TB control, demanding new diagnostic tools. This paper proposes a decision support tool (DST) for screening pulmonary TB (PTB) patients at a secondary clinic. The DST is composed of an adaptive resonance model (iART) for risk group identification (low, medium and high) and a multilayer perceptron (MLP) neural network for classifying patients as active or inactive PTB...
July 2018: Tuberculosis
https://www.readbyqxmd.com/read/30029921/platelet-monocyte-interaction-in-mycobacterium-tuberculosis-infection
#17
Vesla Kullaya, Andre van der Ven, Stellah Mpagama, Blandina T Mmbaga, Philip de Groot, Gibson Kibiki, Quirijn de Mast
The immune effects of platelets and platelet-leukocyte aggregation are increasingly recognized. We studied the occurrence of platelet-monocyte aggregation (PMA) in patients with pulmonary tuberculosis (TB), the processes underlying PMA and consequences for cytokine responses. In a cross-sectional study involving 65 Tanzanian TB patients in different phases of treatment and 29 healthy controls, TB patients had a significantly higher PMA. This increased PMA in TB patients was associated with increased monocyte CCR5, CD16 expression and PF4, but not with increased membrane-expressed or soluble P-selectin expression...
July 2018: Tuberculosis
https://www.readbyqxmd.com/read/30029920/characterization-of-mutations-conferring-streptomycin-resistance-to-multidrug-resistant-mycobacterium-tuberculosis-isolates-from-myanmar
#18
Nan Aye Thida Oo, Lai Lai San, Jeewan Thapa, Khin Saw Aye, Wah Wah Aung, Chie Nakajima, Yasuhiko Suzuki
Numerous studies report that mutations of rpsL (encoding the S12 protein), rrs (encoding 16S rRNA) and gidB (encoding rRNA methyltransferase) are responsible for conferring resistance to streptomycin (STR), which is usually used in both multidrug-resistant tuberculosis (MDR-TB) treatments and re-treatments in Myanmar. The aim of this study was to explore the variation and frequency of mutations in rpsL, rrs and gidB in 141 STR-resistant MDR-TB isolates from Myanmar. Most isolates belonged to the Beijing genotype (105, 74...
July 2018: Tuberculosis
https://www.readbyqxmd.com/read/30029919/proteomic-analysis-reveals-that-sulfamethoxazole-induces-oxidative-stress-in-m-tuberculosis
#19
R Sarkar, C Mdladla, L Macingwana, R-D Pietersen, A H Ngwane, D L Tabb, P D van Helden, I Wiid, B Baker
The emerging resistance of tuberculosis (TB) to current first line drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) warrants alternative treatment approaches with broad-spectrum efficacy. Previously, we have shown that sulfamethoxazole (SMX) has synergestic activity with rifampicin against Mycobacterium tuberculosis. The primary target of SMX is folP1 in mycobacteria; however, SMX may affect other secondary targets in M. tuberculosis. This study investigated the potential additional targets of SMX in a clinical isolate of M...
July 2018: Tuberculosis
https://www.readbyqxmd.com/read/30029918/rs1800796-of-the-il6-gene-is-associated-with-increased-risk-for-anti-tuberculosis-drug-induced-hepatotoxicity-in-chinese-han-children
#20
Yingjia Li, Haijing Tang, Hui Qi, Chen Shen, Lin Sun, Jieqiong Li, Fang Xu, Weiwei Jiao, Xu Yang, Adong Shen
Previous studies have revealed the important contribution of the immune response and oxidative stress to the development of anti-tuberculosis drug-induced hepatotoxicity (ATDH). To investigate whether single-nucleotide polymorphisms (SNPs) of the cytokine gene interleukin-6 (IL6) and oxidative stress genes xanthine dehydrogenase/oxidase (XO) and inducible nitric oxide synthase (NOS2) were associated with susceptibility to ATDH, we performed a case-control study including 41 ATDH cases and 116 ATDH-free controls in Chinese Han children...
July 2018: Tuberculosis
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