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Tuberculosis, antimicrobial drug resistance

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https://www.readbyqxmd.com/read/29663670/analogue-synthesis-reveals-decoupling-of-antibiofilm-and-%C3%AE-lactam-potentiation-activities-of-a-lead-2-aminoimidazole-adjuvant-against-mycobacterium-smegmatis
#1
Sara E Martin, Catherine M Nguyen, Randall J Basaraba, Christian Melander
Biofilm formation is one of the many mechanisms bacteria utilize to survive antibiotic treatment. It has been demonstrated that when Mycobacterium tuberculosis exists in a biofilm in vitro it expresses phenotypic resistance to antimicrobial drugs. Since the in vivo survival of M. tuberculosis following drug treatment is potentially linked to a biofilm-like expression of drug tolerance, it is hypothesized that biofilm dispersion should increase antibiotic susceptibility and reduce the duration of the current antibiotic treatment regimen...
April 16, 2018: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/29653033/organometallic-conjugates-of-the-drug-sulfadoxine-for-combatting-antimicrobial-resistance
#2
Peter J Sadler, Prinessa Chellan, Vicky Avery, Sandra Duffy, James Triccas, Gayathri Nagalingam, Christina Tam, Luisa Cheng, Jenny Liu, Kirkwood Land, Guy Clarkson, Isolda Romero
Fourteen novel arene RuII, and cyclopentadienyl (Cpx) RhIII and IrIII complexes containing an N,N'-chelated pyridylimino- or quinolylimino ligand functionalized with the antimalarial drug sulfadoxine have been synthesized and characterized, including three by x-ray crystallography. Rhodium and iridium complexes exhibited potent antiplasmodial activity with IC50 values of 0.10 - 2.0 µM in either all, or one of the three Plasmodium falciparum assays (3D7 chloroquine sensitive, Dd2 chloroquine resistant and NF54 sexual late stage gametocytes), but were only moderately active towards Trichomonas vaginalis...
April 13, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29619185/examining-the-role-of-protein-structural-dynamics-in-drug-resistance-in-mycobacterium-tuberculosis
#3
Daniel J Shaw, Rachel E Hill, Niall Simpson, Fouad S Husseini, Kirsty Robb, Gregory M Greetham, Michael Towrie, Anthony W Parker, David Robinson, Jonathan D Hirst, Paul A Hoskisson, Neil T Hunt
Antimicrobial resistance represents a growing global health problem. The emergence of novel resistance mechanisms necessitates the development of alternative approaches to investigate the molecular fundamentals of resistance, leading ultimately to new strategies for counteracting them. To gain deeper insight into antibiotic-target interactions, the binding of the frontline anti-tuberculosis drug isoniazid (INH) to a target enzyme, InhA, from Mycobacterium tuberculosis was studied using ultrafast two-dimensional infrared (2D-IR) spectroscopy and molecular simulations...
December 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/29589538/antimicrobial-peptides-for-the-treatment-of-pulmonary-tuberculosis-allies-or-foes
#4
Bruno Rivas-Santiago, Flor Torres-Juarez
Tuberculosis is an ancient disease that has become a serious public health issue in recent years, although increasing incidence has been controlled, deaths caused by Mycobacterium tuberculosis have been accentuated due to the emerging of multi-drug resistant strains and the comorbidity with diabetes mellitus and HIV. This situation is threatening the goals of world health organization (WHO) to eradicate tuberculosis in 2035. WHO has called for the creation of new drugs as an alternative for the treatment of pulmonary tuberculosis, among the plausible molecules that can be used are the antimicrobial peptides (AMPs)...
March 27, 2018: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/29554229/of-testing-and-treatment-implications-of-implementing-new-regimens-for-multidrug-resistant-tuberculosis
#5
David W Dowdy, Grant Theron, Jeffrey A Tornheim, Robin Warren, Emily A Kendall
A novel, shorter-course regimen for treating multidrug-resistant (MDR) tuberculosis was recently recommended by the World Health Organization. However, the most appropriate use of drug susceptibility testing (DST) to support this regimen is less clear. Implementing countries must therefore often choose between using a standardized regimen despite high levels of underlying drug resistance or require more stringent DST prior to treatment initiation. The former carries a high likelihood of exposing patients to de facto monotherapy with a critical drug class (fluoroquinolones), whereas the latter could exclude large groups of patients from their most effective treatment option...
October 1, 2017: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
https://www.readbyqxmd.com/read/29544082/isolation-and-characterization-of-bacteriophages-from-india-with-lytic-activity-against-mycobacterium-tuberculosis
#6
Urmi Bajpai, Abhishek Kumar Mehta, Kandasamy Eniyan, Avni Sinha, Ankita Ray, Simran Virdi, Shazeb Ahmad, Aridni Shah, Deepanksha Arora, Devyani Marwaha, Gunjan Chauhan, Prarthna Saraswat, Punita Bathla, Ruchi Singh
Bacteriophages are being considered as a promising natural resource for the development of alternative strategies against mycobacterial diseases, especially in the context of the wide spread occurrence of drug-resistance amongst the clinical isolates of M. tuberculosis. However, there isn't much information documented on mycobacteriophages from India. Here, we report the isolation of 17 mycobacteriophages using M. smegmatis as the bacterial host where 9 phages also lyse M. tuberculosis H37Rv. We present detailed analysis of one of these mycobacteriophage (PDRPv)...
March 15, 2018: Canadian Journal of Microbiology
https://www.readbyqxmd.com/read/29531418/integrating-tuberculosis-and-antimicrobial-resistance-control-programmes
#7
Rumina Hasan, Sadia Shakoor, Johanna Hanefeld, Mishal Khan
Many low- and middle-income countries facing high levels of antimicrobial resistance, and the associated morbidity from ineffective treatment, also have a high burden of tuberculosis. Over recent decades many countries have developed effective laboratory and information systems for tuberculosis control. In this paper we describe how existing tuberculosis laboratory systems can be expanded to accommodate antimicrobial resistance functions. We show how such expansion in services may benefit tuberculosis case-finding and laboratory capacity through integration of laboratory services...
March 1, 2018: Bulletin of the World Health Organization
https://www.readbyqxmd.com/read/29499834/targeting-bacterial-energetics-to-produce-new-antimicrobials
#8
REVIEW
Kiel Hards, Gregory M Cook
From the war on drug resistance, through cancer biology, even to agricultural and environmental protection: there is a huge demand for rapid and effective solutions to control infections and diseases. The development of small molecule inhibitors was once an accepted "one-size fits all" approach to these varied problems, but persistence and resistance threaten to return society to a pre-antibiotic era. Only five essential cellular targets in bacteria have been developed for the majority of our clinically-relevant antibiotics...
January 2018: Drug Resistance Updates: Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy
https://www.readbyqxmd.com/read/29487047/potential-application-of-digitally-linked-tuberculosis-diagnostics-for-real-time-surveillance-of-drug-resistant-tuberculosis-transmission-validation-and-analysis-of-test-results
#9
Kamela Charmaine Ng, Conor Joseph Meehan, Gabriela Torrea, Léonie Goeminne, Maren Diels, Leen Rigouts, Bouke Catherine de Jong, Emmanuel André
BACKGROUND: Tuberculosis (TB) is the highest-mortality infectious disease in the world and the main cause of death related to antimicrobial resistance, yet its surveillance is still paper-based. Rifampicin-resistant TB (RR-TB) is an urgent public health crisis. The World Health Organization has, since 2010, endorsed a series of rapid diagnostic tests (RDTs) that enable rapid detection of drug-resistant strains and produce large volumes of data. In parallel, most high-burden countries have adopted connectivity solutions that allow linking of diagnostics, real-time capture, and shared repository of these test results...
February 27, 2018: JMIR Medical Informatics
https://www.readbyqxmd.com/read/29467300/high-throughput-metabolomic-analysis-predicts-mode-of-action-of-uncharacterized-antimicrobial-compounds
#10
Mattia Zampieri, Balazs Szappanos, Maria Virginia Buchieri, Andrej Trauner, Ilaria Piazza, Paola Picotti, Sébastien Gagneux, Sonia Borrell, Brigitte Gicquel, Joel Lelievre, Balazs Papp, Uwe Sauer
Rapidly spreading antibiotic resistance and the low discovery rate of new antimicrobial compounds demand more effective strategies for early drug discovery. One bottleneck in the drug discovery pipeline is the identification of the modes of action (MoAs) of new compounds. We have developed a rapid systematic metabolome profiling strategy to classify the MoAs of bioactive compounds. The method predicted MoA-specific metabolic responses in the nonpathogenic bacterium Mycobacterium smegmatis after treatment with 62 reference compounds with known MoAs and different metabolic and nonmetabolic targets...
February 21, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29458544/antimicrobial-activity-against-mycobacterium-tuberculosis-under-in-vitro-lipid-rich-dormancy-conditions
#11
Diana Angelica Aguilar-Ayala, Margo Cnockaert, Peter Vandamme, Juan Carlos Palomino, Anandi Martin, Jorge Gonzalez-Y-Merchand
Although tuberculosis treatment is dependent on drug-susceptibility testing (DST) and molecular drug-resistance detection, treatment failure and relapse remain a challenge. This could be partially due to the emergence of antibiotic-tolerant dormant mycobacteria, where host lipids have been shown to play an important role. This study evaluated the susceptibility of Mycobacterium tuberculosis to two antibiotic combinations - rifampicin, moxifloxacin, amikacin and metronidazole (RIF-MXF-AMK-MTZ), and rifampicin, moxifloxacin, amikacin and pretomanid (RIF-MXF-AMK-PA) - in a lipid-rich dormancy model...
January 15, 2018: Journal of Medical Microbiology
https://www.readbyqxmd.com/read/29454879/application-of-genetically-encoded-redox-biosensors-to-measure-dynamic-changes-in-the-glutathione-bacillithiol-and-mycothiol-redox-potentials-in-pathogenic-bacteria
#12
REVIEW
Quach Ngoc Tung, Nico Linzner, Vu Van Loi, Haike Antelmann
Gram-negative bacteria utilize glutathione (GSH) as their major LMW thiol. However, most Gram-positive bacteria do not encode enzymes for GSH biosynthesis and produce instead alternative LMW thiols, such as bacillithiol (BSH) and mycothiol (MSH). BSH is utilized by Firmicutes and MSH is the major LMW thiol of Actinomycetes. LMW thiols are required to maintain the reduced state of the cytoplasm, but are also involved in virulence mechanisms in human pathogens, such as Staphylococcus aureus, Mycobacterium tuberculosis, Streptococcus pneumoniae, Salmonella enterica subsp...
February 15, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29454844/the-epidemiology-of-febrile-illness-in-sub-saharan-africa-implications-for-diagnosis-and-management
#13
REVIEW
Michael J Maze, Quique Bassat, Nicholas A Feasey, Inácio Mandomando, Patrick Musicha, John A Crump
BACKGROUND: Fever is among the most common symptoms of people living in Africa, and clinicians are challenged by the similar clinical features of a wide spectrum of potential aetiologies. AIM: To summarise recent studies of fever aetiology in sub-Saharan Africa focusing on causes other than malaria. SOURCES: A narrative literature review by searching the MEDLINE database, and recent conference abstracts. CONTENT: Studies of multiple potential causes of fever are scarce, and for many participants the infecting organism remains unidentified, or multiple co-infecting microorganisms are identified, and establishing causation is challenging...
February 15, 2018: Clinical Microbiology and Infection
https://www.readbyqxmd.com/read/29422273/automated-broth-based-systems-versus-the-mycotb-plate-for-antimicrobial-susceptibility-testing-of-the-mycobacterium-tuberculosis-complex-challenges-in-interpretation
#14
Isabella W Martin, Kim Dionne, Sharon M Deml, Nancy L Wengenack, Nicole M Parrish
We examined categorical agreement between automated mycobacterial susceptibility testing methods (Mycobacterial Growth Indicator Tube [MGIT] 960 System and the VersaTREK Mycobacteria Detection and Susceptibility System) which are based on single critical concentration (CC) "breakpoints" and a commercial microbroth dilution method (Sensititre Mycobacterium tuberculosis MIC Plate [MYCOTB]) which provides an MIC value. Mycobacterium tuberculosis isolates (n=355) were tested against three first-line antimycobacterial agents (ethambutol [EMB], isoniazid [INH], rifampin [RIF]) using the MYCOTB plate and either the MGIT 960 (site 1, n=142) or VersaTREK (site 2, n=213) systems...
January 6, 2018: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29382097/nigella-damascena-l-essential-oil-a-valuable-source-of-%C3%AE-elemene-for-antimicrobial-testing
#15
Elwira Sieniawska, Rafal Sawicki, Joanna Golus, Marta Swatko-Ossor, Grazyna Ginalska, Krystyna Skalicka-Wozniak
The most commonly used plant source of β-elemene is Curcuma wenyujin Y. H. Chen & C. Ling (syn. of Curcuma aromatic Salisb.) with its content in supercritical CO₂ extract up to 27.83%. However, the other rich source of this compound is Nigella damascena L. essential oil, in which β-elemene accounts for 47%. In this work, the effective protocol for preparative isolation of β-elemene from a new source-N. damascena essential oil-using high performance counter-current chromatography HPCCC was elaborated...
January 28, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29376490/targeting-dna-repair-systems-in-antitubercular-drug-development
#16
Alina Minias, Anna Brzostek, Jaroslaw Dziadek
Infections with Mycobacterium tuberculosis, the causative agent of tuberculosis, are difficult to treat using currently available chemotherapeutics. Clinicians agree on the urgent need for novel drugs to treat tuberculosis. In this mini review, we summarize data that prompts the consideration of DNA repair-associated proteins as targets for the development of new antitubercular compounds. We discuss data, including gene expression data, that highlight the importance of DNA repair genes during the pathogenic cycle as well as after exposure to antimicrobials currently in use...
January 28, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29367740/combined-chemical-genetics-and-data-driven-bioinformatics-approach-identifies-receptor-tyrosine-kinase-inhibitors-as-host-directed-antimicrobials
#17
Cornelis J Korbee, Matthias T Heemskerk, Dragi Kocev, Elisabeth van Strijen, Omid Rabiee, Kees L M C Franken, Louis Wilson, Nigel D L Savage, Sašo Džeroski, Mariëlle C Haks, Tom H M Ottenhoff
Antibiotic resistance poses rapidly increasing global problems in combatting multidrug-resistant (MDR) infectious diseases like MDR tuberculosis, prompting for novel approaches including host-directed therapies (HDT). Intracellular pathogens like Salmonellae and Mycobacterium tuberculosis (Mtb) exploit host pathways to survive. Only very few HDT compounds targeting host pathways are currently known. In a library of pharmacologically active compounds (LOPAC)-based drug-repurposing screen, we identify multiple compounds, which target receptor tyrosine kinases (RTKs) and inhibit intracellular Mtb and Salmonellae more potently than currently known HDT compounds...
January 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29348586/analogues-of-disulfides-from-allium-stipitatum-demonstrate-potent-anti-tubercular-activities-through-drug-efflux-pump-and-biofilm-inhibition
#18
Cynthia A Danquah, Eleftheria Kakagianni, Proma Khondkar, Arundhati Maitra, Mukhlesur Rahman, Dimitrios Evangelopoulos, Timothy D McHugh, Paul Stapleton, John Malkinson, Sanjib Bhakta, Simon Gibbons
Disulfides from Allium stipitatum, commonly known as Persian shallot, were previously reported to possess antibacterial properties. Analogues of these compounds, produced by S-methylthiolation of appropriate thiols using S-methyl methanethiosulfonate, exhibited antimicrobial activity, with one compound inhibiting the growth of Mycobacterium tuberculosis at 17 µM (4 mg L-1 ) and other compounds inhibiting Escherichia coli and multi-drug-resistant (MDR) Staphylococcus aureus at concentrations ranging between 32-138 µM (8-32 mg L-1 )...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29322464/transcriptional-profiling-mycobacterium-tuberculosis-from-patient-sputa
#19
Leticia Muraro Wildner, Katherine A Gould, Simon J Waddell
The emergence of drug resistance threatens to destroy tuberculosis control programs worldwide, with resistance to all first-line drugs and most second-line drugs detected. Drug tolerance (or phenotypic drug resistance) is also likely to be clinically relevant over the 6-month long standard treatment for drug-sensitive tuberculosis. Transcriptional profiling the response of Mycobacterium tuberculosis to antimicrobial drugs offers a novel interpretation of drug efficacy and mycobacterial drug-susceptibility that likely varies in dynamic microenvironments, such as the lung...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29319341/emerging-mechanisms-of-antimicrobial-resistance-in-bacteria-and-fungi-advances-in-the-era-of-genomics
#20
John Osei Sekyere, Jonathan Asante
Bacteria and fungi continue to develop new ways to adapt and survive the lethal or biostatic effects of antimicrobials through myriad mechanisms. Novel antibiotic resistance genes such as lsa(C), erm(44), VCC-1, mcr-1, mcr-2, mcr-3, mcr-4, bla KLUC-3 and bla KLUC-4 were discovered through comparative genomics and further functional studies. As well, mutations in genes that hitherto were unknown to confer resistance to antimicrobials, such as trm, PP2C, rpsJ, HSC82, FKS2 and Rv2887, were shown by genomics and transcomplementation assays to mediate antimicrobial resistance in Acinetobacter baumannii, Staphylococcus aureus, Enterococcus faecium, Saccharomyces cerevisae, Candida glabrata and Mycobacterium tuberculosis, respectively...
February 2018: Future Microbiology
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