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https://www.readbyqxmd.com/read/28930653/fishing-for-answers-in-human-mycobacterial-infections
#1
Miriam Bolz, Joel D Ernst
Two recent studies (Cambier et al., 2017; Madigan et al., 2017) reveal in vivo functions for specific phenolic glycolipids (PGLs) in the mycobacteria that cause tuberculosis or leprosy. M. tuberculosis (and M. marinum) PGL promotes bacterial spread to growth-permissive macrophages, while M. leprae PGL-1 induces macrophages to cause nerve demyelination characteristic of human leprosy.
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28925956/sulfadiazine-salicylaldehyde-based-schiff-bases-synthesis-antimicrobial-activity-and-cytotoxicity
#2
Martin Krátký, Magdaléna Dzurková, Jiří Janoušek, Klára Konečná, František Trejtnar, Jiřina Stolaříková, Jarmila Vinšová
The resistance among microbes has brought an urgent need for new drugs. Thus, we synthesized a series of Schiff bases derived from the sulfa drug sulfadiazine and various salicylaldehydes. The resulting 4-[(2-hydroxybenzylidene)amino]-N-(pyrimidin-2-yl)benzene-sulfonamides were characterized and evaluated against Gram-positive and Gram-negative bacteria, yeasts, moulds, Mycobacterium tuberculosis, nontuberculous mycobacteria (M. kansasii, M. avium) and their cytotoxicity was determined. Among bacteria, the genus Staphylococcus, including methicillin-resistant S...
September 19, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28925518/chemistry-of-peptidoglycan-in-mycobacterium-tuberculosis-life-style-an-off-the-wall-balance-of-synthesis-and-degradation
#3
Flavia Squeglia, Alessia Ruggiero, Rita Berisio
The cell wall envelope of mycobacteria is structurally distinct from that of both Gram-positive and Gram-negative bacteria. In Mycobacterium tuberculosis, this cell wall has unique structural features and plays a crucial role in drug resistance and macrophage survival under stress conditions. Peptidoglycan is the major constituent of this cell wall, with an important structural role, giving structural strength, and counteracting the osmotic pressure of the cytoplasm. Synthesis of this complex polymer takes place in three stages that occur at three different locations in the cell, from the cytoplasm to the external side of the cell membrane, where polymerization occurs...
September 19, 2017: Chemistry: a European Journal
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
#4
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
#5
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 it with NADPH...
September 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28919338/diagnostic-accuracy-of-xpert-mtb-rif-ultra-for-tuberculous-meningitis-in-hiv-infected-adults-a-prospective-cohort-study
#6
Nathan C Bahr, Edwin Nuwagira, Emily E Evans, Fiona V Cresswell, Philip V Bystrom, Adolf Byamukama, Sarah C Bridge, Ananta S Bangdiwala, David B Meya, Claudia M Denkinger, Conrad Muzoora, David R Boulware
BACKGROUND: WHO recommends Xpert MTB/RIF as initial diagnostic testing for tuberculous meningitis. However, diagnosis remains difficult, with Xpert sensitivity of about 50-70% and culture sensitivity of about 60%. We evaluated the diagnostic performance of the new Xpert MTB/RIF Ultra (Xpert Ultra) for tuberculous meningitis. METHODS: We prospectively obtained diagnostic cerebrospinal fluid (CSF) specimens during screening for a trial on the treatment of HIV-associated cryptococcal meningitis in Mbarara, Uganda...
September 14, 2017: Lancet Infectious Diseases
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
#7
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/28910983/quantitative-proteomic-analysis-of-host-responses-triggered-by-mycobacterium-tuberculosis-infection-in-human-macrophage-cells
#8
Hua Li, Sha Wei, Yuan Fang, Min Li, Xia Li, Zhe Li, Jibin Zhang, Guofeng Zhu, Chuanyou Li, Lijun Bi, Guimin Zhang, Dianbing Wang, Xian-En Zhang
Macrophages are primary host of Mycobacterium tuberculosis (M.tb) and the central effector of in vivo innate immune responses against bacteria. Though the interaction between macrophages and mycobacteria has been widely investigated, the molecular mechanisms of M.tb pathogenesis in macrophages are still not clear. In this work, we investigated the altered protein expression profiles of macrophages after virulent H37Rv strain and avirulent H37Ra strain infection by tandem mass tag-based quantitative proteomics...
September 1, 2017: Acta Biochimica et Biophysica Sinica
https://www.readbyqxmd.com/read/28904991/bioelectrospray-methodology-for-dissection-of-the-host-pathogen-interaction-in-human-tuberculosis
#9
Liku B Tezera, Magdalena K Bielecka, Paul T Elkington
Standard cell culture models have been used to investigate disease pathology and to test new therapies for over fifty years. However, these model systems have often failed to mimic the changes occurring within three-dimensional (3-D) space where pathology occurs in vivo. To truthfully represent this, an emerging paradigm in biology is the importance of modelling disease in a physiologically relevant 3-D environment. One of the approaches for 3-D cell culture is bioelectrospray technology. This technique uses an alginate-based 3-D environment as an inert backbone within which mammalian cells and extracellular matrix can be incorporated...
July 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28902922/molecular-clustering-of-patients-with-diabetes-and-pulmonary-tuberculosis-a-systematic-review-and-meta-analysis
#10
Francles Blanco-Guillot, Guadalupe Delgado-Sánchez, Norma Mongua-Rodríguez, Pablo Cruz-Hervert, Leticia Ferreyra-Reyes, Elizabeth Ferreira-Guerrero, Mercedes Yanes-Lane, Rogelio Montero-Campos, Miriam Bobadilla-Del-Valle, Pedro Torres-González, Alfredo Ponce-de-León, José Sifuentes-Osornio, Lourdes Garcia-Garcia
INTRODUCTION: Many studies have explored the relationship between diabetes mellitus (DM) and tuberculosis (TB) demonstrating increased risk of TB among patients with DM and poor prognosis of patients suffering from the association of DM/TB. Owing to a paucity of studies addressing this question, it remains unclear whether patients with DM and TB are more likely than TB patients without DM to be grouped into molecular clusters defined according to the genotype of the infecting Mycobacterium tuberculosis bacillus...
2017: PloS One
https://www.readbyqxmd.com/read/28900018/distinct-spatiotemporal-dynamics-of-peptidoglycan-synthesis-between-mycobacterium%C3%A2-smegmatis-and-mycobacterium%C3%A2-tuberculosis
#11
Helene Botella, Guangli Yang, Ouathek Ouerfelli, Sabine Ehrt, Carl F Nathan, Julien Vaubourgeix
Peptidoglycan (PG), a polymer cross-linked by d-amino acid-containing peptides, is an essential component of the bacterial cell wall. We found that a fluorescent d-alanine analog (FDAA) incorporates chiefly at one of the two poles in Mycobacterium smegmatis but that polar dominance varies as a function of the cell cycle in Mycobacterium tuberculosis: immediately after cytokinesis, FDAAs are incorporated chiefly at one of the two poles, but just before cytokinesis, FDAAs are incorporated comparably at both. These observations suggest that mycobacterial PG-synthesizing enzymes are localized in functional compartments at the poles and septum and that the capacity for PG synthesis matures at the new pole in M...
September 12, 2017: MBio
https://www.readbyqxmd.com/read/28893784/the-dual-mechanism-of-action-of-5-nitro-1-10-phenanthroline-against-mycobacterium-tuberculosis
#12
Saqib Kidwai, Chan-Yong Park, Shradha Mawatwal, Prabhakar Tiwari, Myung Geun Jung, Tannu Priya Gosain, Pradeep Kumar, David Alland, Sandeep Kumar, Avinash Bajaj, Yun-Kyung Hwang, Chang Sik Song, Rohan Dhiman, Ill Young Lee, Ramandeep Singh
New chemotherapeutics agents with novel mechanism of action are urgently required to combat the challenge imposed by the emergence of drug resistant mycobacteria. In this study, a phenotypic whole cell screen identified 5-nitro-1,10-phenanthroline (5NP) as a lead compound. 5NP resistant isolates harbored mutations mapped to fbiB and were also resistant to bicyclic nitroimidazole, PA-824. Mechanistic studies confirmed that 5NP is activated in F420 dependent manner resulting in formation of 1,10-phenanthroline and 1,10-phenanthrolin-5-amine as major metabolites in bacteria...
September 11, 2017: Antimicrobial Agents and Chemotherapy
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
#13
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
#14
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
#15
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
#16
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/28875176/lactoferricin-peptides-increase-macrophages-capacity-to-kill-mycobacterium-avium
#17
Tânia Silva, Ana C Moreira, Kamran Nazmi, Tânia Moniz, Nuno Vale, Maria Rangel, Paula Gomes, Jan G M Bolscher, Pedro N Rodrigues, Margarida Bastos, Maria Salomé Gomes
Mycobacterial infections cause a significant burden of disease and death worldwide. Their treatment is long, toxic, costly, and increasingly prone to failure due to bacterial resistance to currently available antibiotics. New therapeutic options are thus clearly needed. Antimicrobial peptides represent an important source of new antimicrobial molecules, both for their direct activity and for their immunomodulatory potential. We have previously reported that a short version of the bovine antimicrobial peptide lactoferricin with amino acids 17 to 30 (LFcin17-30), along with its variants obtained by specific amino acid substitutions, killed Mycobacterium avium in broth culture...
July 2017: MSphere
https://www.readbyqxmd.com/read/28873466/rational-design-of-drug-like-compounds-targeting-mycobacterium-marinum-melf-protein
#18
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
#19
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/28870005/in-vitro-effect-of-dfc-2-on-the-mycolic-acid-biosynthesis-in-mycobacteriumtuberculosis
#20
Sukyung Kim, Hoonhee Seo, Hafij Al Mahmud, Md Imtiazul Islam, Yong-Sik Kim, Jiwon Lyu, Kung-Woo Nam, Byung-Eui Lee, Kee-In Lee, Ho-Yeon Song
DFC-2, a methyl 5-[2-(dimethylamino)ethoxy]-7,12-dioxo-7,12-dihydrodinaphtho[1,2-b:2',3'-d]furan-6-carboxylate, is reported to have antitubercular effects against Mycobacterium tuberculosis. At concentrations ranging from 0.19 to 0.39 µg/ml, DFC-2 inhibited both drug-susceptible and -resistant strains of M. tuberculosis. Microarray analyses were employed to gain insights into the molecular mechanisms of DFC-2's action in M. tuberculosis. The most affected functional gene category was "lipid biosynthesis", which is involved in mycolic acid synthesis...
September 5, 2017: Journal of Microbiology and Biotechnology
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