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https://www.readbyqxmd.com/read/28933243/drug-targets-in-dormant-mycobacterium-tuberculosis-can-the-conquest-against-tuberculosis-become-a-reality
#1
Vivek Kumar Gupta, M Madhan Kumar, Dharmendra Singh, Deepa Bisht, Shweta Sharma
Targeting M. tuberculosis (Mtb) in latent form of infection is a major obstacle and big challenge in tuberculosis (TB) eradication by current chemotherapy. A better understanding of the physiology of Mtb and of the metabolic state of the bacillus during the dormancy, is a primary need in finding drug targets against non replicating persistent (NRP) form of the Mtb. Identification of potential drug targets against dormant state of Mtb is critically important to achieve the goal of complete eradication for shortening of anti-TB therapy...
September 21, 2017: Infectious Diseases
https://www.readbyqxmd.com/read/28931915/non-tuberculous-mycobacteria-isolated-from-pulmonary-samples-in-sub-saharan-africa-a-systematic-review-and-meta-analyses
#2
Catherine Okoi, Suzanne T B Anderson, Martin Antonio, Sarah N Mulwa, Florian Gehre, Ifedayo M O Adetifa
Pulmonary non-tuberculous mycobacterial (NTM) disease epidemiology in sub-Saharan Africa is not as well described as for pulmonary tuberculosis. Earlier reviews of global NTM epidemiology only included subject-level data from one sub-Saharan Africa country. We systematically reviewed the literature and searched PubMed, Embase, Popline, OVID and Africa Wide Information for articles on prevalence and clinical relevance of NTM detection in pulmonary samples in sub-Saharan Africa. We applied the American Thoracic Society/Infectious Disease Society of America criteria to differentiate between colonisation and disease...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28919618/molecular-detection-and-differentiation-of-mycobacterium-tuberculosis-complex-and-non-tuberculous-mycobacterium-in-the-clinical-specimens-by-real-time-pcr
#3
M M Rahman, M R Rahim, A Khaled, T A Nasir, F Nasrin, M A Hasan
Mycobacteria are subdivided into three groups: the Mycobacterium tuberculosis complex, the non-tuberculous mycobacteria called NTM or MOTT (Mycobacteria Other Than Tuberculosis) and Mycobacterium leprae. Over the past few decades, the incidence of infections caused by NTM has increased world wide. The differentiation of Mycobacterium tuberculosis complex from NTM is of primary importance for infection control and choice of antimicrobial therapy. However, there is so far no report in Bangladesh about the detection of NTM and hence differentiation of MTB and NTM...
July 2017: Mymensingh Medical Journal: MMJ
https://www.readbyqxmd.com/read/28919416/identification-of-eukaryotic-udp-galactopyranose-mutase-inhibitors-using-the-thermofad-assay
#4
Julia S Martín Del Campo, Meital Eckshtain-Levi, Pablo Sobrado
Aspergillus fumigatus is a human pathogen responsible for deadly infections in immune-compromised patients. A potential strategy for treating A. fumigatus infections is by targeting the biosynthesis of cell wall components, such as galactofuranase, which is absent in humans. Galactofuranose biosynthesis is initiated by the flavoenzyme UDP-galactopyranose mutase (UGM), which converts UDP-galactopyranose (UDP-Galp) to UDP-galactofuranose (UDP-Galf). UGM requires the reduced form of the flavin for activity, which is obtained by reacting with NADPH...
September 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28917089/the-trehalose-specific-transporter-lpqy-sugabc-is-required-for-antimicrobial-and-anti-biofilm-activity-of-trehalose-analogues-in-mycobacterium-smegmatis
#5
Jeffrey M Wolber, Bailey L Urbanek, Lisa M Meints, Brent F Piligian, Irene C Lopez-Casillas, Kailey M Zochowski, Peter J Woodruff, Benjamin M Swarts
Mycobacteria, including the bacterial pathogen that causes human tuberculosis, possess distinctive pathways for synthesizing and utilizing the non-mammalian disaccharide trehalose. Trehalose metabolism is essential for mycobacterial viability and has been linked to in vitro biofilm formation, which may bear relevance to in vivo drug tolerance. Previous research has shown that some trehalose analogues bearing modifications at the 6-position inhibit growth of various mycobacterial species. In this work, 2-, 5-, and 6-position-modified trehalose analogues were synthesized using our previously reported one-step chemoenzymatic method and shown to inhibit growth and biofilm formation in the two-to three-digit micromolar range in Mycobacterium smegmatis...
August 9, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/28893193/light-emitting-diode-fluorescent-microscopy-and-xpert-mtb-rif%C3%A2-assay-for-diagnosis-of-pulmonary-tuberculosis-among-patients-attending-ambo-hospital-west-central-ethiopia
#6
Alemu Gadissa Gelalcha, Abebaw Kebede, Hassen Mamo
BACKGROUND: The relatively simple and cheaper light-emitting diode fluorescent microscopy (LED-FM) was recommended by the World Health Organization (WHO) to replace the conventional tuberculosis (TB) microscopy in both high- and low-volume laboratories. More recently the WHO also endorsed one more technique, Xpert MTB/RIF® assay (Xpert), for improved TB diagnosis particularly among human immunodeficiency virus (HIV)-infected cases. However, the relative performance of both of these tools differs from setting to setting in reference to the conventional TB diagnostics...
September 11, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28886145/application-of-a-whole-blood-mycobacterial-growth-inhibition-assay-to-study-immunity-against-mycobacterium-tuberculosis-in-a-high-tuberculosis-burden-population
#7
Richard Baguma, Adam Penn-Nicholson, Erica Smit, Mzwandile Erasmus, Jonathan Day, Lebohang Makhethe, Marwou de Kock, E Jane Hughes, Michele van Rooyen, Bernadette Pienaar, Lynnett Stone, Willem Hanekom, Michael J Brennan, Robert S Wallis, Mark Hatherill, Thomas J Scriba
The determinants of immunological protection against Mycobacterium tuberculosis (M.tb) infection in humans are not known. Mycobacterial growth inhibition assays have potential utility as in vitro surrogates of in vivo immunological control of M.tb. We evaluated a whole blood growth inhibition assay in a setting with high burden of TB and aimed to identify immune responses that correlate with control of mycobacterial growth. We hypothesized that individuals with underlying M.tb infection will exhibit greater M...
2017: PloS One
https://www.readbyqxmd.com/read/28879160/performance-of-xpert-%C3%A2-mtb-rif-among-tuberculosis-outpatients-in-lilongwe-malawi
#8
Tarsizio Chikaonda, Nelson Nguluwe, Brian Barnett, Runa H Gokhale, Robert Krysiak, Isaac Thengolose, Nora E Rosenberg, Christopher Stanley, James Mpunga, Irving F Hoffman, Mina Hosseinipour, Lesley Scott, Wendy Stevens
BACKGROUND: Xpert(®) MTB/RIF is a molecular test for the detection of Mycobacterium tuberculosis and rifampicin resistance. It is considered to be a great advance over smear microscopy and culture. However, there is very little information regarding the performance characteristics of Xpert MTB/RIF in Malawi. OBJECTIVE: We aimed to evaluate the performance of Xpert MTB/RIF in a Malawian setting. METHODS: Stored sputum pellets were processed on Xpert MTB/RIF between June 2012 and May 2014...
2017: African Journal of Laboratory Medicine
https://www.readbyqxmd.com/read/28879157/evaluation-of-the-sd-bioline-tb-ag-mpt64-test-for-identification-of-mycobacterium-tuberculosis-complex-from-liquid-cultures-in-southwestern-uganda
#9
Patrick Orikiriza, Dan Nyehangane, Daniel Atwine, John J Kisakye, Kennedy Kassaza, Juliet-Mwanga Amumpaire, Yap Boum
BACKGROUND: To confirm presence of Mycobacterium tuberculosis complex, some tuberculosis culture laboratories still rely on para-nitrobenzoic acid (PNB), a traditional technique that requires sub-culturing of clinical isolates and two to three weeks to give results. Rapid identification tests have improved turnaround times for mycobacterial culture results. Considering the challenges of the PNB method, we assessed the performance of the SD Bioline TB Ag MPT64 assay by using PNB as gold standard to detect M...
2017: African Journal of Laboratory Medicine
https://www.readbyqxmd.com/read/28873466/rational-design-of-drug-like-compounds-targeting-mycobacterium-marinum-melf-protein
#10
Renu Dharra, Sakshi Talwar, Yogesh Singh, Rani Gupta, Jeffrey D Cirillo, Amit K Pandey, Mahesh Kulharia, Promod K Mehta
The mycobacterial mel2 locus (mycobacterial enhanced infection locus, Rv1936-1941) is Mycobacterium marinum and M. tuberculosis specific, which can withstand reactive oxygen species (ROS) and reactive nitrogen species (RNS) induced stress. A library of over a million compounds was screened using in silico virtual ligand screening (VLS) to identify inhibitors against the modeled structure of MelF protein expressed by melF of mel2 locus so that M. marinum's ability to withstand ROS/RNS stress could be reduced...
2017: PloS One
https://www.readbyqxmd.com/read/28870736/role-of-rifampin-for-the-treatment-of-bacterial-infections-other-than-mycobacteriosis
#11
REVIEW
Chun-Yuan Lee, Chung-Hao Huang, Po-Liang Lu, Wen-Chien Ko, Yen-Hsu Chen, Po-Ren Hsueh
OBJECTIVES: Rifampin was initially approved for the treatment of tuberculosis. Because of its low toxicity, broad-spectrum activity, and good bioavailability, rifampin is now commonly administered as combination antimicrobial therapy for the treatment of various infections caused by organisms other than mycobacteria. This review summarizes the most recent clinical studies on the use of rifampin combinations for treating four common non-mycobacterial infections: acute bacterial meningitis, infective endocarditis and bacteraemia, pneumonia, and biofilm-related infections...
September 1, 2017: Journal of Infection
https://www.readbyqxmd.com/read/28855835/distribution-of-non-tuberculosis-mycobacteria-strains-from-suspected-tuberculosis-patients-by-heat-shock-protein-65-pcr-rflp
#12
Ali Nour-Neamatollahie, Nayereh Ebrahimzadeh, Seyed Davar Siadat, Farzam Vaziri, Mona Eslami, Abbas Akhavan Sepahi, Sharareh Khanipour, Morteza Masoumi, Fatemeh Sakhaee, Morteza Ghazanfari Jajin, Ahmadreza Bahrmand, Abolfazl Fateh
The genus Mycobacterium contains more than 150 species. Non-tuberculosis mycobacteria (NTM) often cause extrapulmonary and pulmonary disease. Mycobacteria detection at species level is necessary and provides useful information on epidemiology and facilitates successful treatment of patients. This retrospective study aimed to determine the incidence of the NTM isolates and Mycobacterium tuberculosis (Mtb) in clinical specimens collected from Iranian patients during February 2011-December 2013, by PCR-restriction fragment length polymorphism analysis (PRA) of the hsp65 gene...
September 2017: Saudi Journal of Biological Sciences
https://www.readbyqxmd.com/read/28841870/molecular-characterization-of-bovine-tuberculosis-strains-in-two-slaughterhouses-in-morocco
#13
Hind Yahyaoui-Azami, Hamid Aboukhassib, Mohammed Bouslikhane, Jaouad Berrada, Soukaina Rami, Miriam Reinhard, Sebastien Gagneux, Julia Feldmann, Sonia Borrell, Jakob Zinsstag
BACKGROUND: Bovine tuberculosis (BTB) is caused by Mycobacterium bovis, which belongs to the Mycobacterium tuberculosis complex. Mycobacterium bovis have been described to be responsible of most cases of bovine tuberculosis. Although M. tuberculosis, M. africanum and non-complex mycobacteria were isolated from cattle. In Morocco, so far, no molecular studies were conducted to characterize the strains responsible of BTB. The present study aims to characterize M. bovis in Morocco. The present study was conducted in slaughterhouses in Rabat and El Jadida...
August 25, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28835629/metabolic-activity-of-mature-biofilms-of-mycobacterium-tuberculosis-and-other-non-tuberculous-mycobacteria
#14
Anna Solokhina, David Brückner, Gernot Bonkat, Olivier Braissant
Mycobacteria are classified into two groups, fast- and slow-growing. Often, fast-growing mycobacteria are assumed to have a higher metabolic activity than their slower counterparts, but in mature biofilms this assumption might not be correct. Indeed, when measuring the metabolic activity of mycobacterial biofilms with two independent non-invasive techniques (isothermal microcalorimetry and tunable diode laser absorption spectrometry), mature biofilms of slow- and fast-growing species appeared more alike than expected...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28821621/protein-kinase-g-confers-survival-advantage-to-mycobacterium-tuberculosis-during-latency-like-conditions
#15
Mehak Zahoor Khan, Ashima Bhaskar, Sandeep Upadhyay, Pooja Kumari, Raju S Rajmani, Preeti Jain, Amit Singh, Dhiraj Kumar, Neel Sarovar Bhavesh, Vinay Kumar Nandicoori
Protein Kinase G (PknG), a thioredoxin-fold containing eukaryotic like serine/threonine protein kinase (STPK), is a virulence factor in the Mycobacterium tuberculosis, required for inhibition of phago-lysosomal fusion. Here, we unravelled novel functional facets of PknG during latency like conditions. We find that PknG mediates persistence under stressful conditions like hypoxia and abets drug tolerance. PknG mutant displayed minimal growth in nutrient limiting conditions suggesting its role in modulating cellular metabolism...
August 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28756649/rnomic-identification-and-evaluation-of-npctb_6715-a-non-protein-coding-rna-gene-as-a-potential-biomarker-for-the-detection-of-mycobacterium-tuberculosis
#16
Priyatharisni Kanniappan, Siti Aminah Ahmed, Ganeswrie Rajasekaram, Citartan Marimuthu, Ewe Seng Ch'ng, Li Pin Lee, Carsten A Raabe, Timofey S Rozhdestvensky, Thean Hock Tang
Technological advances in RNA biology greatly improved transcriptome profiling during the last two decades. Besides the discovery of many small RNAs (sRNA) that are involved in the physiological and pathophysiological regulation of various cellular circuits, it becomes evident that the corresponding RNA genes might also serve as potential biomarkers to monitor the progression of disease and treatment. sRNA gene candidate npcTB_6715 was previously identified via experimental RNomic (unpublished data), and we report its application as potential biomarker for the detection of Mycobacterium tuberculosis (MTB) in patient samples...
July 29, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28723969/matrixlysis-an-improved-sample-preparation-method-for-recovery-of-mycobacteria-from-animal-tissue-material
#17
Christoph Leth, Ashok Varadharajan, Patrick Mester, Marlis Fischaleck, Peter Rossmanith, Friedrich Schmoll, Maria Fink
Mycobacterium caprae, a member of the Mycobacterium tuberculosis complex, is the main causative agent of bovine tuberculosis in alpine regions. Bacterial culture is the gold standard in bovine tuberculosis diagnostic but takes up to twelve weeks. This increases the time and costs for stocks affected with bovine tuberculosis. Hence this study focused on the implementation of a fast and precise mycobacterial detection method and compared it with currently used methods. Matrix lysis is a chemical lysis using high concentrations of urea to solubilize bovine and red deer tissue and was used to detect even smallest amounts or non-visible lesions of mycobacteria...
2017: PloS One
https://www.readbyqxmd.com/read/28719821/bcg-old-workhorse-new-skills
#18
REVIEW
M Gengenbacher, N E Nieuwenhuizen, She Kaufmann
Bacille Calmette-Guérin (BCG), the only tuberculosis (TB) vaccine in clinical practice, has limitations in efficacy, immunogenicity and safety. Much current TB vaccine research focuses on engineering live mycobacteria to interfere with phagosome biology and host intracellular pathways including apoptosis and autophagy, with candidates such as BCG Δzmp1, BCG ΔureC::hly, BCG::ESX-1(Mmar), Mtb ΔphoP ΔfadD26, Mtb ΔRD1 ΔpanCD and M. smegmatis Δesx-3::esx-3(Mtb) in the development pipeline. Correlates of protection in preclinical studies include increased central memory CD4(+) T cells and recruitment of antigen-specific T cells to the lungs, with mucosal vaccination found to be superior to parenteral vaccination...
July 15, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28709494/multiple-abdominal-abscesses-a-not-so-common-presentation-of-ntm
#19
Darshan K Bajaj, R A S Kushwaha, Anand Srivastava, Mona Asnani
Non-tuberculous Mycobacteria/Mycobacterium other than tuberculosis (MOTT) are ubiquitous organisms. They are acid fast bacilli often giving trouble to the physician to distinguish it from Mycobacterium tuberculosis. These organisms are a menace for the treating physician as when to treat and when not to treat. They are often difficult to diagnose and may present in a variety of forms with propensity to cause number of infections of different body parts and organs. They are more common in immunocompromised individuals e...
July 2017: Indian Journal of Tuberculosis
https://www.readbyqxmd.com/read/28696241/ethambutol-partitioning-in-tuberculous-pulmonary-lesions-explains-its-clinical-efficacy
#20
Matthew Zimmerman, Jodi Lestner, Brendan Prideaux, Paul O'Brien, Isabela Dias-Freedman, Chao Chen, Jillian Dietzold, Isaac Daudelin, Firat Kaya, Landry Blanc, Pei-Yu Chen, Steven Park, Padmini Salgame, Jansy Sarathy, Véronique Dartois
Clinical trials and practice have shown that ethambutol is an important component of the first-line tuberculosis (TB) regime. This contrasts the drug's rather modest potency and lack of activity against nongrowing persister mycobacteria. The standard plasma-based pharmacokinetic-pharmacodynamic profile of ethambutol suggests that the drug may be of limited clinical value. Here, we hypothesized that this apparent contradiction may be explained by favorable penetration of the drug into TB lesions. First, we utilized novel in vitro lesion pharmacokinetic assays and predicted good penetration of the drug into lesions...
September 2017: Antimicrobial Agents and Chemotherapy
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