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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
#1
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/28440326/complex-multifractal-nature-in-mycobacterium-tuberculosis-genome
#2
Saurav Mandal, Tanmoy Roychowdhury, Keilash Chirom, Alok Bhattacharya, R K Brojen Singh
The mutifractal and long range correlation (C(r)) properties of strings, such as nucleotide sequence can be a useful parameter for identification of underlying patterns and variations. In this study C(r) and multifractal singularity function f(α) have been used to study variations in the genomes of a pathogenic bacteria Mycobacterium tuberculosis. Genomic sequences of M. tuberculosis isolates displayed significant variations in C(r) and f(α) reflecting inherent differences in sequences among isolates. M. tuberculosis isolates can be categorised into different subgroups based on sensitivity to drugs, these are DS (drug sensitive isolates), MDR (multi-drug resistant isolates) and XDR (extremely drug resistant isolates)...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28438994/latently-and-uninfected-healthcare-workers-exposed-to-tb-make-protective-antibodies-against-mycobacterium-tuberculosis
#3
Hao Li, Xing-Xing Wang, Bin Wang, Lei Fu, Guan Liu, Yu Lu, Min Cao, Hairong Huang, Babak Javid
The role of Igs in natural protection against infection by Mycobacterium tuberculosis (Mtb), the causative agent of TB, is controversial. Although passive immunization with mAbs generated against mycobacterial antigens has shown protective efficacy in murine models of infection, studies in B cell-depleted animals only showed modest phenotypes. We do not know if humans make protective antibody responses. Here, we investigated whether healthcare workers in a Beijing TB hospital-who, although exposed to suprainfectious doses of pathogenic Mtb, remain healthy-make antibody responses that are effective in protecting against infection by Mtb...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438933/pyrazinoic-acid-inhibits-a-bifunctional-enzyme-in-mycobacterium-tuberculosis
#4
Moses Njire, Na Wang, Bangxing Wang, Yaoju Tan, Xingshan Cai, Yanwen Liu, Julius Mugweru, Jintao Guo, H M Adnan Hameed, Shouyong Tan, Jianxiong Liu, Wing Wai Yew, Eric Nuermberger, Gyanu Lamichhane, Jinsong Liu, Tianyu Zhang
Pyrazinamide (PZA), an indispensable component of modern tuberculosis treatment, acts as a key sterilizing drug. While the mechanism of activation of this prodrug by Mycobacterium tuberculosis into pyrazinoic acid (POA) has been extensively studied, not all molecular determinants that confer resistance to this mysterious drug have been identified. Here, we report a new PZA resistance determinant: Asp67Asn substitution in Rv2783 confers M. tuberculosis resistance to PZA. Expression of the mutant but not the wild-type allele in M...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438925/identification-of-mycobacterial-genes-involved-in-antibiotic-sensitivity-implications-in-the-treatment-of-tuberculosis-with-%C3%AE-lactam-containing-regimens
#5
Gopinath Viswanathan, Sangya Yadav, Tirumalai R Raghunand
In a Mycobacterium smegmatis mutant library screen, transposon mutants with insertions in fhaA, dprE2, rpsT and parA, displayed hypersusceptibility to antibiotics including the β-lactams meropenem, ampicillin, amoxicillin and cefotaxime. Sub MIC levels of octoclothepin, a psychotic drug inhibiting ParA, phenocopied the parA insertion and enhanced the bactericidal activity of meropenem against Mycobacteriumtuberculosis in combination with clavulanate. Our study identifies novel factors associated with antibiotic resistance, with implications in repurposing β-lactams for tuberculosis treatment...
April 24, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28438643/convenient-pcr-method-for-variable-number-tandem-repeat-typing-of-mycobacterium-tuberculosis-clinical-isolates
#6
Junji Seto, Takayuki Wada, Yu Suzuki, Tatsuya Ikeda, Katsumi Mizuta, Satoshi Mitarai, Tadayuki Ahiko
Variable-number tandem-repeat typing for Mycobacterium tuberculosis clinical isolates contributes to evidence-based tuberculosis control. However, cumbersome PCR procedures for the typing have disturbed routine analyses. We proposed a convenient PCR method for the typing using a PCR master mix that provides rapidity and long-term stability of the frozen PCR cocktail.
April 21, 2017: Journal of Microbiological Methods
https://www.readbyqxmd.com/read/28438553/human-leukocyte-antigen-class-i-a-b-and-c-allele-and-haplotype-variation-in-a-south-african-mixed-ancestry-population
#7
Shayne Loubser, Maria Paximadis, Caroline T Tiemessen
South Africa has a large (∼53 million), ethnically diverse population (black African, Caucasian, Indian/Asian and Mixed ancestry) and a high disease burden (particularly HIV-1 and Mycobacterium tuberculosis). The Mixed ancestry population constitutes ∼9% of the total population and was established ∼365 years ago in the Western Cape region through interracial mixing of black Africans, Europeans and Asians. Admixed populations present unique opportunities to identify genetic factors involved in disease susceptibility...
April 21, 2017: Human Immunology
https://www.readbyqxmd.com/read/28438221/isolated-splenic-tuberculosis-with-subsequent-paradoxical-deterioration-a-case-report
#8
Frederick Wangai, Loice Achieng, George Otieno, Jacqueline Njoroge, Tabitha Wambaire, Jamilla Rajab
BACKGROUND: Isolated tuberculosis of the spleen has been described occasionally in literature, mostly in immunosuppressed individuals with various risk factors. Sequestration in the spleen makes such Mycobacterium tuberculosis infection difficult to diagnose. This report describes an extremely rare case of isolated splenic tuberculosis in an immunocompetent individual. CASE PRESENTATION: A 26 year old Kenyan male presented with pyrexia of unknown origin, with negative screening tests for bacterial, fungal and parasitic infections...
April 24, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28438117/reproducibility-of-african-giant-pouched-rats-detecting-mycobacterium-tuberculosis
#9
Haylee Ellis, Christiaan Mulder, Emilio Valverde, Alan Poling, Timothy Edwards
BACKGROUND: African pouched rats sniffing sputum samples provided by local clinics have significantly increased tuberculosis case findings in Tanzania and Mozambique. The objective of this study was to determine the reproducibility of rat results. METHODS: Over an 18-month period 11,869 samples were examined by the rats. Intra-rater reliability was assessed through Yule's Q. Inter-rater reliability was assessed with Krippendorff's alpha. RESULTS: Intra-rater reliability was high, with a mean Yule's Q of 0...
April 24, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28436493/an-attenuated-mycobacterium-tuberculosis-clinical-strain-with-a-defect-in-esx-1-secretion-induces-minimal-host-immune-responses-and-pathology
#10
Helena Strand Clemmensen, Niels Peter Hell Knudsen, Erik Michael Rasmussen, Jessica Winkler, Ida Rosenkrands, Ahmad Ahmad, Troels Lillebaek, David R Sherman, Peter Lawætz Andersen, Claus Aagaard
Although Mycobacterium tuberculosis (M.tb) DK9897 is an attenuated strain, it was isolated from a patient with extrapulmonary tuberculosis and vaccination with a subunit vaccine (H56) induced poor protection against it. Both attenuation and lack of protection are because M.tb DK9897 cannot secrete the EsxA virulence factor nor induce a host response against it. Genome sequencing identified a frameshift mutation in the eccCa1 gene. Since the encoded EccCa1 protein provides energy for ESX-1 secretion, it suggested a defect in the ESX-1 type VII secretion system...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436453/functional-thermodynamics-structural-and-biological-studies-of-in-silico-identified-inhibitors-of-mycobacterium-tuberculosis-enoyl-acp-coa-reductase-enzyme
#11
Leonardo K B Martinelli, Mariane Rotta, Anne D Villela, Valnês S Rodrigues-Junior, Bruno L Abbadi, Rogério V Trindade, Guilherme O Petersen, Giuliano M Danesi, Laura R Nery, Ivani Pauli, Maria M Campos, Carla D Bonan, Osmar Norberto de Souza, Luiz A Basso, Diogenes S Santos
Novel chemotherapeutics agents are needed to kill Mycobacterium tuberculosis, the main causative agent of tuberculosis (TB). The M. tuberculosis 2-trans-enoyl-ACP(CoA) reductase enzyme (MtInhA) is the druggable bona fide target of isoniazid. New chemotypes were previously identified by two in silico approaches as potential ligands to MtInhA. The inhibition mode was determined by steady-state kinetics for seven compounds that inhibited MtInhA activity. Dissociation constant values at different temperatures were determined by protein fluorescence spectroscopy...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28435012/il-10-down-regulates-the-expression-of-survival-associated-gene-hspx-of-mycobacterium-tuberculosis-in-murine-macrophage
#12
Babban Jee, Pawan Sharma, Kiran Katoch, Beenu Joshi, Sudhir Kumar Awasthi
Mycobacterium tuberculosis (MTB) adopts a special survival strategy to overcome the killing mechanism(s) of host immune system. Amongst the many known factors, small heat shock protein 16.3 (sHSP16.3) of MTB encoded by gene hspX has been reported to be critical for the survival of MTB. In the present study, the effect of recombinant murine interferon-gamma (rmIFN-γ) and recombinant murine interleukin-10 (rmIL-10) on the expression of gene hspX of MTB in murine macrophage RAW264.7 has been investigated. By real-time RT-PCR, it was observed that three increasing concentrations (5, 25 and 50ng/ml) of rmIFN-γ significantly up-regulated the expression of hspX whereas similar concentrations of rmIL-10 (5, 25 and 50ng/ml) significantly down-regulated the hspX expression...
April 20, 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28434972/one-bacillus-to-rule-them-all-investigating-broad-range-host-adaptation-in-mycobacterium-bovis
#13
REVIEW
Adrian R Allen
Recent advances are permitting researchers to undertake largescale comparative genomics studies within and between bacterial species to determine the types of genetic change that underpin the phenotypic spectrum that runs from strict host adaptation to generalist. Within the Mycobacterium tuberculosis complex (MTBC) of bacilli, there is much heterogeneity in host specificity. Globally, Mycobacterium bovis exhibits a broad host range encompassing domesticated bovine and wildlife animals unlike the human adapted specialist M...
April 20, 2017: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/28434937/defining-a-research-agenda-to-address-the-converging-epidemics-of-tuberculosis-and-diabetes-part-2-underlying-biological-mechanisms
#14
REVIEW
Katharina Ronacher, Reinout van Crevel, Julia Critchley, Andrew A Bremer, Larry S Schlesinger, Anil Kapur, Randall Basaraba, Hardy Kornfeld, Blanca I Restrepo
There is growing interest in the re-emerging interaction between type 2 diabetes (DM) and tuberculosis (TB), but the underlying biological mechanisms are poorly understood despite their possible implications in clinical management. Experts in epidemiological, public health, basic science and clinical studies recently convened and identified research priorities for elucidating the underlying mechanisms for the co-ocurrence of TB and DM. We identified gaps in current knowlege of altered immunity in DM patients during TB, where most studies suggest an under-performing innate immunity, but exaggerated adaptive immunity to Mycobacterium tuberculosis...
April 19, 2017: Chest
https://www.readbyqxmd.com/read/28433210/non-tuberculous-mycobacteria-an-emerging-threat
#15
Susana Martínez González, Arantxa Cano Cortés, Luis Alfonso Sota Yoldi, José María García García, Luz María Alba Álvarez, Juan José Palacios Gutiérrez
INTRODUCTION AND OBJECTIVE: Non-tuberculous mycobacteria (NTM) isolates are becoming more common. The main objective of our study was to establish the number and diversity of NTM species in our region and their distribution according to the source sample, age and gender of the patients, and to analyse clinically significant isolates. METHODOLOGY: Prospective study of all NTM isolated in Asturias from 2005 to 2012. Samples were processed following internationally accepted guidelines...
April 19, 2017: Archivos de Bronconeumología
https://www.readbyqxmd.com/read/28432345/distant-phe345-mutation-compromises-the-stability-and-activity-of-mycobacterium-tuberculosis-isocitrate-lyase-by-modulating-its-structural-flexibility
#16
Harish Shukla, Rohit Shukla, Amit Sonkar, Tripti Pandey, Timir Tripathi
Isocitrate lyase (ICL), a potential anti-tubercular drug target, catalyzes the first step of the glyoxylate shunt. In the present investigation, we studied the conformational flexibility of MtbICL to better understand its stability and catalytic activity. Our biochemical results showed that a point mutation at Phe345, which is topologically distant (>10 Å) to the active site signature sequence ((189)KKCGH(193)), completely abolishes the activity of the enzyme. In depth computational analyses were carried out for understanding the structural alterations using molecular dynamics, time-dependent secondary structure and principal component analysis...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28432321/mycobacterium-tuberculosis-lineage-distribution-in-xinjiang-and-gansu-provinces-china
#17
Haixia Chen, Li He, Hairong Huang, Chengmin Shi, Xumin Ni, Guangming Dai, Liang Ma, Weimin Li
Mycobacterium tuberculosis (M. tuberculosis) genotyping has dramatically improved the understanding of the epidemiology of tuberculosis (TB). In this study, 187 M. tuberculosis isolates from Xinjiang Uygur Autonomous Region (Xinjiang) and Gansu province in China were genotyped using large sequence polymorphisms (LSPs) and variable number tandem repeats (VNTR). Ten isolates, which represent major nodes of VNTR-based minimum spanning tree, were selected and subsequently subjected to multi-locus sequence analyses (MLSA) that include 82 genes...
April 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28431548/water-pipe-smoke-condensate-increases-the-internalization-of-mycobacterium-bovis-of-type-ii-alveolar-epithelial-cells-a549
#18
Esmaeil Mortaz, Shamila D Alipoor, Masoud Movassaghi, Mohammad Varahram, Jahangir Ghorbani, Gert Folkerts, Johan Garssen, Ian M Adcock
BACKGROUND: Tuberculosis (TB) is a major global health problem, and there is an association between tobacco smoke and TB. Water pipe smoking has become an increasing problem not only in Middle Eastern countries but also globally because users consider it as safer than cigarettes. The presence of high levels of toxic substances in water-pipe smoke may be a predisposing factor that enhances the incidence of pulmonary disorders. For example, uncontrolled macropinocytosis in alveolar epithelial cells following exposure to water-pipe smoke may predispose subjects to pulmonary infection...
April 21, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28430824/suppressors-of-cytokine-signaling-in-tuberculosis
#19
Shih-Wei Lee, Chi-Wei Liu, Jia-Ying Hu, Li-Mei Chiang, Chih-Pin Chuu, Lawrence Shih-Hsin Wu, Yung-Hsi Kao
Tuberculosis (TB), a global disease mainly infected by Mycobacterium tuberculosis, remains leading public health problem worldwide. Suppressors of cytokine signaling (SOCSs) play important roles in the protection against microbial infection. However, the relationship between members of the SOCS family and tuberculosis infection remains unclear. Using peripheral blood mononuclear cells, we investigated the mRNA expression profiles of SOCS subfamilies among active TB, latent tuberculosis infection (LTBI), and healthy individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28430807/diagnosis-of-smear-negative-tuberculosis-is-greatly-improved-by-xpert-mtb-rif
#20
Giulia Lombardi, Valentina Di Gregori, Nicolò Girometti, Marina Tadolini, Francesco Bisognin, Paola Dal Monte
BACKGROUND: Diagnosis of pulmonary (PTB) and extra-pulmonary tuberculosis (EPTB) in smear-negative patients can be difficult. We assessed retrospectively the performance of Xpert MTB/RIF system (Xpert, Cepheid) in diagnosing smear-negative tuberculosis (TB), which represents the most common form of TB in a low incidence setting. METHODS: Performance of Xpert was compared to acid-fast microscopic examination using Ziehl-Neelsen (ZN) stain in patients with culture-confirmed TB...
2017: PloS One
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