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https://www.readbyqxmd.com/read/28340510/the-diverse-family-of-mmpl-transporters-in-mycobacteria-from-regulation-to-antimicrobial-developments
#1
REVIEW
Albertus Viljoen, Violaine Dubois, Fabienne Girard-Misguich, Mickael Blaise, Jean-Louis Herrmann, Laurent Kremer
Mycobacterial genomes contain large sets of loci encoding membrane proteins that belong to a family of multidrug resistance pumps designated Resistance-Nodulation-Cell Division (RND) permeases. Mycobacterial membrane protein Large (MmpL) transporters represent a subclass of RND transporters known to participate in the export of lipid components across the cell envelope. These surface-exposed lipids with unusual structures play key roles in the physiology of mycobacteria and/or can act as virulence factors and immunomodulators...
March 24, 2017: Molecular Microbiology
https://www.readbyqxmd.com/read/28340368/synthesis-molecular-docking-antimycobacterial-and-antimicrobial-evaluation-of-new-pyrrolo-3-2-c-pyridine-mannich-bases
#2
Gilish Jose, Tholappanavara H Suresha Kumara, Haliwana B V Sowmya, Dharmarajan Sriram, Tayur N Guru Row, Amar A Hosamani, Sunil S More, Bhavya Janardhan, B G Harish, Sandeep Telkar, Yalegara Siddappa Ravikumar
In this report, we describe the synthesis and biological evaluation of a new series of pyrrolo[3,2-c]pyridine Mannich bases (7a-v). The Mannich bases were obtained in good yields by one-pot three component condensation of pyrrolo[3,2-c]pyridine scaffold (6a-c) with secondary amines and excess of formaldehyde solution in AcOH. The chemical structures of the compounds were characterized by (1)H NMR, (13)C NMR, LC/MS and elemental analysis. Single crystal X-ray diffraction has been recorded for compound 7k ([C23H29ClN4](+2), H2O)...
March 16, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28335571/3-substituted-n-benzylpyrazine-2-carboxamide-derivatives-synthesis-antimycobacterial-and-antibacterial-evaluation
#3
Lucia Semelková, Ondřej Janďourek, Klára Konečná, Pavla Paterová, Lucie Navrátilová, František Trejtnar, Vladimír Kubíček, Jiří Kuneš, Martin Doležal, Jan Zitko
A series of substituted N-benzyl-3-chloropyrazine-2-carboxamides were prepared as positional isomers of 5-chloro and 6-chloro derivatives, prepared previously. During the aminolysis of the acyl chloride, the simultaneous substitution of chlorine with benzylamino moiety gave rise to N-benzyl-3-(benzylamino)pyrazine-2-carboxamides as side products, in some cases. Although not initially planned, the reaction conditions were modified to populate this double substituted series. The final compounds were tested against four mycobacterial strains...
March 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28335544/combination-effect-of-antituberculosis-drugs-and-ethanolic-extract-of-selected-medicinal-plants-against-multi-drug-resistant-mycobacterium-tuberculosis-isolates
#4
Prabasiwi Nur Fauziyah, Elin Yulinah Sukandar, Dhyan Kusuma Ayuningtyas
Adverse drug reaction and resistance to antituberculosis drugs remain the causes of tuberculosis therapeutic failure. This research aimed to find the combination effect of standard antituberculosis drugs with Hibiscus sabdariffa L., Kaempferia galanga L., and Piper crocatum N.E. Br against multi-drug resistant (MDR) Mycobacterium tuberculosis isolates. Two MDR strains (i.e., isoniazid/ethambutol resistant and rifampicin/streptomycin resistant) of M. tuberculosis were inoculated in Löwenstein-Jensen medium containing a combination of standard antituberculosis drugs and ethanolic extracts of H...
March 20, 2017: Scientia Pharmaceutica
https://www.readbyqxmd.com/read/28334803/statistical-analysis-of-genetic-interactions-in-tn-seq-data
#5
Michael A DeJesus, Subhalaxmi Nambi, Clare M Smith, Richard E Baker, Christopher M Sassetti, Thomas R Ioerger
Tn-Seq is an experimental method for probing the functions of genes through construction of complex random transposon insertion libraries and quantification of each mutant's abundance using next-generation sequencing. An important emerging application of Tn-Seq is for identifying genetic interactions, which involves comparing Tn mutant libraries generated in different genetic backgrounds (e.g. wild-type strain versus knockout strain). Several analytical methods have been proposed for analyzing Tn-Seq data to identify genetic interactions, including estimating relative fitness ratios and fitting a generalized linear model...
February 22, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334194/swga-a-primer-design-toolkit-for-selective-whole-genome-amplification
#6
Erik L Clarke, Sesh A Sundararaman, Stephanie N Seifert, Frederic D Bushman, Beatrice H Hahn, Dustin Brisson
Motivation: Population genomic analyses are often hindered by difficulties in obtaining sufficient numbers of genomes for analysis by DNA sequencing. Selective whole-genome amplification (SWGA) provides an efficient approach to amplify microbial genomes from complex backgrounds for sequence acquisition. However, the process of designing sets of primers for this method has many degrees of freedom and would benefit from an automated process to evaluate the vast number of potential primer sets...
February 27, 2017: Bioinformatics
https://www.readbyqxmd.com/read/28334088/relapse-re-infection-and-mixed-infections-in-tuberculosis-disease
#7
Amanda McIvor, Hendrik Koornhof, Bavesh Davandra Kana
Tuberculosis (TB) disease can be characterized by genotypic and phenotypic complexity in Mycobacterium tuberculosis bacilli within a single patient. This microbiological heterogeneity has become an area of intense study due its perceived importance in drug tolerance, drug resistance and as a surrogate measure of transmission rates. This review presents a descriptive analysis of research describing the prevalence of mixed strain TB infections in geographically distinct locations. Despite significant variation in disease burden and a rampant HIV-TB co-epidemic, there was no difference in the prevalence range of mixed infections reported in African countries when compared to the rest of the world...
February 18, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28333978/association-between-genotype-and-drug-resistance-profiles-of-mycobacterium-tuberculosis-strains-circulating-in-china-in-a-national-drug-resistance-survey
#8
Yang Zhou, Susan van den Hof, Shengfen Wang, Yu Pang, Bing Zhao, Hui Xia, Richard Anthony, Xichao Ou, Qiang Li, Yang Zheng, Yuanyuan Song, Yanlin Zhao, Dick van Soolingen
We describe the population structure of a representative collection of 3,133 Mycobacterium tuberculosis isolates, collected within the framework of a national resistance survey from 2007 in China. Genotyping data indicate that the epidemic strains in China can be divided into seven major complexes, of which 92% belonged to the East Asian (mainly Beijing strains) or the Euro-American lineage. The epidemic Beijing strains in China are closely related to the Beijing B0/W148 strain earlier described in Russia and a large cluster of these strains has spread national wide...
2017: PloS One
https://www.readbyqxmd.com/read/28333945/environmental-reservoirs-of-pathogenic-mycobacteria-across-the-ethiopian-biogeographical-landscape
#9
Hayley C King, Tanya Khera-Butler, Phillip James, Brian B Oakley, Girume Erenso, Abraham Aseffa, Rob Knight, Elizabeth M Wellington, Orin Courtenay
The Mycobacterium genus comprises over one-hundred-and-fifty recognised species, the majority of which reside in the environment and many of which can be pathogenic to mammals. Some species of environmental mycobacteria may interfere with BCG vaccination efficacy and in tuberculin test interpretation. Examining biogeographic trends in the distribution of members of the mycobacteria across a number of physicochemical and spatial gradients in soil and water environments across Ethiopia using oligotyping identified differential distributions of pathogenic and significant species...
2017: PloS One
https://www.readbyqxmd.com/read/28333913/tuberculosis-among-foreign-born-persons-diagnosed-%C3%A2-10-years-after-arrival-in-the-united-states-2010-2015
#10
Clarisse A Tsang, Adam J Langer, Thomas R Navin, Lori R Armstrong
The majority of tuberculosis (TB) cases in the United States are attributable to reactivation of latent TB infection (LTBI) (1). LTBI refers to the condition when a person is infected with Mycobacterium tuberculosis without signs and symptoms, or radiographic or bacteriologic evidence of TB disease. CDC and the U.S. Preventive Services Task Force (USPSTF) recommend screening populations at increased risk for LTBI, including persons who have lived in congregate settings at high risk and persons who were born in, or are former residents of countries with TB incidence ≥20 cases per 100,000 population (2-4)...
March 24, 2017: MMWR. Morbidity and Mortality Weekly Report
https://www.readbyqxmd.com/read/28333342/activity-of-faropenem-with-and-without-rifampicin-against-mycobacterium-tuberculosis-evaluation-in-a-whole-blood-bactericidal-activity-trial
#11
Meera Gurumurthy, Rupangi Verma, Claire M Naftalin, Kim Hor Hee, Qingshu Lu, Kin Hup Tan, Simi Issac, Wenwei Lin, Angelia Tan, Kok-Yong Seng, Lawrence Soon-U Lee, Nicholas I Paton
Background: Faropenem has in vitro activity against Mycobacterium tuberculosis (Mtb) and shows synergy with rifampicin. We tested this in a whole-blood bactericidal activity (WBA) trial. Methods: We randomized healthy volunteers to receive a single oral dose of faropenem (600 mg) with amoxicillin/clavulanic acid (500/125 mg) ( n  =   8), rifampicin (10 mg/kg) ( n  =   14) or the combination rifampicin + faropenem + amoxicillin/clavulanic acid ( n  =   14)...
March 18, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28333192/susceptibilities-of-mdr-mycobacterium-tuberculosis-isolates-to-unconventional-drugs-compared-with-their-reported-pharmacokinetic-pharmacodynamic-parameters
#12
Joseph S Cavanaugh, Ruwen Jou, Mei-Hua Wu, Tracy Dalton, Ekaterina Kurbatova, Julia Ershova, J Peter Cegielski
Background: The second-line drugs recommended to treat drug-resistant TB are toxic, expensive and difficult to procure. Given increasing resistance, the need for additional anti-TB drugs has become more urgent. But new drugs take time to develop and are expensive. Some commercially available drugs have reported anti-mycobacterial activity but are not routinely used because supporting laboratory and clinical evidence is sparse. Methods: We analysed 217 MDR M. tuberculosis isolates including 153 initial isolates from unique patients and 64 isolates from follow-up specimens during the course of treatment...
February 20, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28332618/the-chemokine-receptor-cxcr4-promotes-granuloma-formation-by-sustaining-a-mycobacteria-induced-angiogenesis-programme
#13
Vincenzo Torraca, Claudia Tulotta, B Ewa Snaar-Jagalska, Annemarie H Meijer
CXC chemokine receptor 4 plays a critical role in chemotaxis and leukocyte differentiation. Furthermore, there is increasing evidence that links this receptor to angiogenesis. Using the well-established zebrafish-Mycobacterium marinum model for tuberculosis, angiogenesis was recently found to be important for the development of cellular aggregates called granulomas that contain the mycobacteria and are the hallmark of tuberculosis disease. Here, we found that initiation of the granuloma-associated proangiogenic programme requires CXCR4 signalling...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28332241/toll-like-receptor-2-arg753gln-and-arg677trp-polymorphisms-and-susceptibility-to-pulmonary-and-peritoneal-tuberculosis
#14
Mohammed A Saleh, Mahmoud M Ramadan, Eman O Arram
Recent evidence suggests that toll-like receptor-2 (TLR2) is important for host defense against Mycobacterium tuberculosis (MTB). TLR2 polymorphisms have shown significant impact on susceptibility or resistance to tuberculosis (TB). This case-control study aims to determine the influence of TLR2 (Arg753Gln and Arg677Trp) polymorphisms on the susceptibility to develop pulmonary or peritoneal TB. Genotyping of TLR2 (Arg753Gln and Arg677Trp) polymorphisms was carried out on 52 patients with pulmonary TB, 44 patients with peritoneal TB, and 50 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)...
March 23, 2017: APMIS: Acta Pathologica, Microbiologica, et Immunologica Scandinavica
https://www.readbyqxmd.com/read/28331837/public-health-relevance-of-non-tuberculous-mycobacteria-among-afb-positive-sputa
#15
Prabha Desikan, Karuna Tiwari, Nikita Panwalkar, Saima Khaliq, Manju Chourey, Reeta Varathe, Shaina Beg Mirza, Arun Sharma, Sridhar Anand, Manoj Pandey
BACKGROUND: Sputum smear microscopy for acid fast bacilli (AFB) is used by most public health programmes to detect tuberculosis. While most AFB in countries endemic for tuberculosis are Mycobacterium tuberculosis (MTB), some may also be non-tuberculous mycobacteria (NTM). The inability to differentiate NTM from MTB by sputum smear microscopy may lead to erroneous diagnoses of tuberculosis, leading in turn to inappropriate therapy. METHODS: This was a retrospective study of consecutive sputum samples received from November 2013 to March 2015 in the Department of Microbiology, Bhopal Memorial Hospital & Research Centre, Bhopal, India...
March 2017: Germs
https://www.readbyqxmd.com/read/28331796/an-unexpected-finding-in-a-man-with-multiple-pulmonary-nodules-a-pleural-effusion-and-respiratory-failure
#16
Yik Lam Pang, Quentin Jones
We report the case of a 47-year old Caucasian man with a history of depression and high alcohol intake who presented with a one-month history of weight loss, dry cough and abdominal pain. He had no smoking history of note. The patient was treated for a suspected chest infection, however developed respiratory failure and was intubated. A CT showed multiple pulmonary nodules, left pleural thickening extending to the mediastinum and bilateral pleural effusions-larger on the left, suggestive of disseminated malignancy...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28331348/molecular-detection-of-multidrug-resistant-tuberculosis-among-smear-positive-pulmonary-tuberculosis-patients-in-jigjiga-town-ethiopia
#17
Mussie Brhane, Ameha Kebede, Yohannes Petros
BACKGROUND: Molecular methods that target drug resistance mutations are suitable approaches for rapid drug susceptibility testing to detect multidrug-resistant tuberculosis (MDR-TB). The aim of the study was to determine MDR-TB cases and to analyze the frequency of gene mutations associated with rifampicin (RIF) and/or isoniazid (INH) resistance of Mycobacterium tuberculosis among smear-positive pulmonary tuberculosis patients. METHODS: Institution-based cross-sectional study design was employed...
2017: Infection and Drug Resistance
https://www.readbyqxmd.com/read/28330892/in-vitro-susceptibility-testing-of-tedizolid-against-nontuberculous-mycobacteria
#18
Barbara A Brown-Elliott, Richard J Wallace
Tedizolid is a new oxazolidinone with improved in vitro and intracellular potency against Mycobacterium tuberculosis, including multidrug resistant strains, and some species of nontuberculous mycobacteria (NTM) compared with linezolid.Using the current Clinical and Laboratory Standards Institute (CLSI) recommended method of broth microdilution, susceptibility testing of 170 isolates of rapidly growing mycobacteria showed equivalent or lower (1- to 8-fold MIC50 and/or MIC90 values) for tedizolid compared to linezolid...
March 22, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28330890/direct-detection-of-rifampicin-and-isoniazid-resistance-in-sputum-samples-from-tuberculosis-patients-by-high-resolution-melt-curve-analysis
#19
Divya Anthwal, Rakesh Kumar Gupta, Manpreet Bhalla, Shinjini Bhatnagar, Jaya Sivaswami Tyagi, Sagarika Haldar
Drug-resistant tuberculosis (TB) is a major threat for TB control worldwide. Globally, only 40% of the 340,000 notified TB patients estimated to have multidrug resistant-TB (MDR-TB) were detected in 2015. This study was carried out to evaluate the utility of High Resolution Melt curve analysis (HRM) for the rapid and direct detection of MDR-TB in Mycobacterium tuberculosis (M. tb) in sputum samples. A reference plasmid library was first generated of the most frequently observed mutations in the resistance determining regions of rpoB, katG and inhA promoter and used as positive controls in HRM...
March 22, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28330178/emergence-of-mixed-infection-of-beijing-non-beijing-strains-among-multi-drug-resistant-mycobacterium-tuberculosis-in-pakistan
#20
Samar Mustafa, Hasnain Javed, Jawairia Hashmi, Nazia Jamil, Zarfishan Tahir, Abdul Majeed Akhtar
Tuberculosis (TB) remains as one of the deadliest diseases after HIV globally with 95 % of deaths confined to low-and-middle income countries. Pakistan is fifth among the 22 high-burden TB countries with the incidence rate of 230/100,000 persons, however, studies related to prevalent Mycobacterium tuberculosis strains and their spread, drug resistance pattern and evolutionary genetics are inadequate. The present study was undertaken to highlight the circulation of M. tuberculosis strains causing drug resistant TB in our community by targeting the molecular marker IS6110 and then characterization of these strains as Beijing and Non-Beijing genotypes...
June 2016: 3 Biotech
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