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Tuberculosis, antimicrobial drug resistance

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https://www.readbyqxmd.com/read/28528648/copper-and-antibiotics-discovery-modes-of-action-and-opportunities-for-medicinal-applications
#1
Alex G Dalecki, Cameron L Crawford, Frank Wolschendorf
Copper is a ubiquitous element in the environment as well as living organisms, with its redox capabilities and complexation potential making it indispensable for many cellular functions. However, these same properties can be highly detrimental to prokaryotes and eukaryotes when not properly controlled, damaging many biomolecules including DNA, lipids, and proteins. To restrict free copper concentrations, all bacteria have developed mechanisms of resistance, sequestering and effluxing labile copper to minimize its deleterious effects...
2017: Advances in Microbial Physiology
https://www.readbyqxmd.com/read/28528545/discovery-and-biosynthesis-of-gladiolin-a-burkholderia-gladioli-antibiotic-with-promising-activity-against-mycobacterium-tuberculosis
#2
Lijiang Song, Matthew Jenner, Joleen Masschelein, Cerith Jones, Matthew J Bull, Simon R Harris, Ruben C Hartkoorn, Anthony Vocat, Isolda Romero-Canelón, Paul Coupland, Gordon Webster, Matthew Dunn, Rebecca Weiser, Christopher Paisey, Stewart T Cole, Julian Parkhill, Eshwar Mahenthiralingam, Gregory L Challis
An antimicrobial activity screen of Burkholderia gladioli BCC0238, a clinical isolate from a cystic fibrosis patient, led to the discovery of gladiolin, a novel macrolide antibiotic with potent activity against Mycobacterium tuberculosis H37Rv. Gladiolin is structurally-related to etnangien, a highly unstable antibiotic from Sorangium cellulosum that is also active against Mycobacteria. Like etnangien, gladiolin was found to inhibit RNA polymerase, a validated drug target in M. tuberculosis. However, gladiolin lacks the highly labile hexaene moiety of etnangien and was thus found to possess significantly increased chemical stability...
May 22, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28512703/metal-homeostasis-in-bacteria-the-role-of-arsr-smtb-family-of-transcriptional-repressors-in-combating-varying-metal-concentrations-in-the-environment
#3
REVIEW
Rudra P Saha, Saikat Samanta, Surajit Patra, Diganta Sarkar, Abinit Saha, Manoj Kumar Singh
Bacterial infections cause severe medical problems worldwide, resulting in considerable death and loss of capital. With the ever-increasing rise of antibiotic-resistant bacteria and the lack of development of new antibiotics, research on metal-based antimicrobial therapy has now gained pace. Metal ions are essential for survival, but can be highly toxic to organisms if their concentrations are not strictly controlled. Through evolution, bacteria have acquired complex metal-management systems that allow them to acquire metals that they need for survival in different challenging environments while evading metal toxicity...
May 16, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28479509/analysis-of-rrs-gene-mutations-in-amikacin-resistant-clinical-isolates-of-mycobacterium-tuberculosis-from-khyber-pakhtunkhwa-pakistan
#4
Kafeel Ahmad, Zeeshan Ahmad, Ramla Somayya, Amjad Ali, Shaista Rahat
Tuberculosis is a major infectious disease caused by Mycobacterium tuberculosis complex. Antimicrobial drugs are used to control TB infections. Molecular mechanisms controlling resistance to second-line drugs are not completely understood and no endogenous information is available regarding these mechanisms. The present study reports mutational analysis of rrs gene in Mycobacterium tuberculosis isolates collected from Khyber Pakhtunkhwa province of Pakistan. A total of 499 Mycobacterium tuberculosis isolates were analyzed for resistance against amikacin...
May 4, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28463485/nitroimidazoles-molecular-fireworks-that-combat-a-broad-spectrum-of-infectious-diseases
#5
Chee Wei Ang, Angie M Jarrad, Matthew A Cooper, Mark A T Blaskovich
Infectious diseases claim millions of lives every year, but with the advent of drug resistance, therapeutic options to treat infections are inadequate. There is now an urgent need to develop new and effective treatments. Nitroimidazoles are a class of antimicrobial drugs that have remarkable broad spectrum activity against parasites, mycobacteria, and anaerobic Gram-positive and Gram-negative bacteria. While nitroimidazoles were discovered in the 1950s, there has been renewed interest in their therapeutic potential, particularly for the treatment of parasitic infections and tuberculosis...
May 22, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28416555/mycobacterium-tuberculosis-proteome-response-to-anti-tuberculosis-compounds-reveals-metabolic-escape-pathways-that-prolong-bacterial-survival
#6
Lia Danelishvili, Natalia Shulzhenko, Jessica J J Chinison, Lmar Babrak, Jialu Hu, Andriy Morgun, Gregory Burrows, Luiz E Bermudez
Tuberculosis (TB) continues to be one of the most common bacterial infectious diseases and the leading cause of death in many parts of the world. A major limitation of TB therapy is slow killing of infecting organism, increasing the risk for the development of tolerance phenotype and drug-resistance. Studies indicate that M. tuberculosis (Mtb) takes several days to be killed upon treatment with lethal concentrations of antibiotics both in vitro and in vivo To investigate how metabolic remodeling can enable transient bacterial survival during exposure with bactericidal concentrations of compounds, Mtb H37Rv strain was exposed to twice of the minimal inhibitory concentration of isoniazid, rifampicin, moxifloxacin, mefloquine or bedaquiline for 24h, 48h, 4 days, and 6 days, and the bacterial proteomic response was analyzed using the quantitative shotgun mass spectrometry...
April 17, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28369307/antimicrobial-resistance-in-mycobacterium-tuberculosis-mechanistic-and-evolutionary-perspectives
#7
Sebastian M Gygli, Sonia Borrell, Andrej Trauner, Sebastien Gagneux
Antibiotic-resistant Mycobacterium tuberculosis strains are threatening progress in containing the global tuberculosis epidemic. Mycobacterium tuberculosis is intrinsically resistant to many antibiotics, limiting the number of compounds available for treatment. This intrinsic resistance is due to a number of mechanisms including a thick, waxy, hydrophobic cell envelope and the presence of drug degrading and modifying enzymes. Resistance to the drugs which are active against M. tuberculosis is, in the absence of horizontally transferred resistance determinants, conferred by chromosomal mutations...
May 1, 2017: FEMS Microbiology Reviews
https://www.readbyqxmd.com/read/28365981/evaluation-of-the-antimicrobial-activity-of-cationic-polymers-against-mycobacteria-toward-antitubercular-macromolecules
#8
Daniel J Phillips, James Harrison, Sarah-Jane Richards, Daniel E Mitchell, Esther Tichauer, Alasdair T M Hubbard, Collette Guy, Ian Hands-Portman, Elizabeth Fullam, Matthew I Gibson
Antimicrobial resistance is a global healthcare problem with a dwindling arsenal of usable drugs. Tuberculosis, caused by Mycobacterium tuberculosis, requires long-term combination therapy and multi- and totally drug resistant strains have emerged. This study reports the antibacterial activity of cationic polymers against mycobacteria, which are distinguished from other Gram-positive bacteria by their unique cell wall comprising a covalently linked mycolic acid-arabinogalactan-peptidoglycan complex (mAGP), interspersed with additional complex lipids which helps them persist in their host...
May 8, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28344011/the-epidemiology-pathogenesis-transmission-diagnosis-and-management-of-multidrug-resistant-extensively-drug-resistant-and-incurable-tuberculosis
#9
REVIEW
Keertan Dheda, Tawanda Gumbo, Gary Maartens, Kelly E Dooley, Ruth McNerney, Megan Murray, Jennifer Furin, Edward A Nardell, Leslie London, Erica Lessem, Grant Theron, Paul van Helden, Stefan Niemann, Matthias Merker, David Dowdy, Annelies Van Rie, Gilman K H Siu, Jotam G Pasipanodya, Camilla Rodrigues, Taane G Clark, Frik A Sirgel, Aliasgar Esmail, Hsien-Ho Lin, Sachin R Atre, H Simon Schaaf, Kwok Chiu Chang, Christoph Lange, Payam Nahid, Zarir F Udwadia, C Robert Horsburgh, Gavin J Churchyard, Dick Menzies, Anneke C Hesseling, Eric Nuermberger, Helen McIlleron, Kevin P Fennelly, Eric Goemaere, Ernesto Jaramillo, Marcus Low, Carolina Morán Jara, Nesri Padayatchi, Robin M Warren
Global tuberculosis incidence has declined marginally over the past decade, and tuberculosis remains out of control in several parts of the world including Africa and Asia. Although tuberculosis control has been effective in some regions of the world, these gains are threatened by the increasing burden of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis. XDR tuberculosis has evolved in several tuberculosis-endemic countries to drug-incurable or programmatically incurable tuberculosis (totally drug-resistant tuberculosis)...
March 15, 2017: Lancet Respiratory Medicine
https://www.readbyqxmd.com/read/28340510/the-diverse-family-of-mmpl-transporters-in-mycobacteria-from-regulation-to-antimicrobial-developments
#10
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/28338408/clofazimine-encapsulation-in-nanoporous-silica-particles-for-the-oral-treatment-of-antibiotic-resistant-mycobacterium-tuberculosis-infections
#11
Sabrina Valetti, Xin Xia, Joana Costa-Gouveia, Priscille Brodin, Marie-Françoise Bernet-Camard, Margareta Andersson, Adam Feiler
AIM: First extensive reformulation of clofazimine (CLZ) in nanoporous silica particles (NSPs) for tackling antibiotic-resistant tuberculosis (TB) infections. MATERIALS & METHODS: Solid-state characterization of several CLZ-encapsulated NSP formulations was followed by in vitro drug solubility, Caco-2 intestinal cells drug permeability and TB antibacterial activity. RESULTS: NSPs stabilize the amorphous state of CLZ (shelf stability >6 months) and dramatically increase the drug solubility in simulated gastric fluid (up to 20-fold) with different dissolution kinetics depending on the NSPs used...
March 24, 2017: Nanomedicine
https://www.readbyqxmd.com/read/28331043/world-health-organization-treatment-guidelines-for-drug-resistant-tuberculosis-2016-update
#12
Dennis Falzon, Holger J Schünemann, Elizabeth Harausz, Licé González-Angulo, Christian Lienhardt, Ernesto Jaramillo, Karin Weyer
Antimicrobial resistance is a major global concern. Tuberculosis (TB) strains resistant to rifampicin and other TB medicines challenge patient survival and public health. The World Health Organization (WHO) has published treatment guidelines for drug-resistant TB since 1997 and last updated them in 2016 based on reviews of aggregated and individual patient data from published and unpublished studies. An international expert panel formulated recommendations following the GRADE approach. The new WHO guidelines recommend a standardised 9-12 months shorter treatment regimen as first choice in patients with multidrug- or rifampicin-resistant TB (MDR/RR-TB) strains not resistant to fluoroquinolones or second-line injectable agents; resistance to these two classes of core second-line medicines is rapidly detectable with molecular diagnostics also approved by WHO in 2016...
March 2017: European Respiratory Journal: Official Journal of the European Society for Clinical Respiratory Physiology
https://www.readbyqxmd.com/read/28327043/handwashing
#13
Erin Dean
Essential facts Antimicrobial resistance develops when medicines are used inappropriately. Global estimates suggest that every year more than 700,000 people die from drug-resistant strains of common bacterial and viral infections, such as tuberculosis, malaria and HIV. If antimicrobial resistance continues to increase, this number could rise to 10 million a year by 2050.
March 22, 2017: Nursing Standard
https://www.readbyqxmd.com/read/28317028/mycobacterial-caseinolytic-protease-gene-regulator-clgr-is-a-substrate-of-caseinolytic-protease
#14
Yoshiyuki Yamada, Thomas Dick
The mycobacterial caseinolytic protease ClpP1P2 is a degradative protease that recently gained interest as a genetically and pharmacologically validated drug target for tuberculosis. The first whole-cell active ClpP1P2 inhibitor, the human proteasome inhibitor bortezomib, is currently undergoing lead optimization to introduce selectivity for the bacterial target. How inhibition of ClpP1P2 translates into whole-cell antimicrobial activity is little understood. Previous work has shown that the caseinolytic protease gene regulator ClgR is an activator of the clpP1P2 genes and also suggested that this transcription factor may be a substrate of the protease...
March 2017: MSphere
https://www.readbyqxmd.com/read/28292983/origins-of-combination-therapy-for-tuberculosis-lessons-for-future-antimicrobial-development-and-application
#15
REVIEW
Christopher A Kerantzas, William R Jacobs
Tuberculosis is a global health problem that causes the death of approximately 1.5 million people worldwide each year (WHO, p. 1-126, Global Tuberculosis Report, 2015). Treatment of drug-susceptible tuberculosis requires combination antimicrobial therapy with a minimum of four antimicrobial agents applied over the course of 6 months. The first instance of combination antimicrobial therapy applied to tuberculosis was the joint use of streptomycin and para-aminosalicylic acid as documented by the Medical Research Council of the United Kingdom in 1950...
March 14, 2017: MBio
https://www.readbyqxmd.com/read/28281443/central-nervous-system-tuberculosis
#16
John M Leonard
Central nervous system tuberculosis (CNS-TB) takes three clinical forms: meningitis (TBM), intracranial tuberculoma, and spinal arachnoiditis. TBM predominates in the western world and presents as a subacute to chronic meningitis syndrome with a prodrome of malaise, fever, and headache progressing to altered mentation and focal neurologic signs, followed by stupor, coma, and death within five to eight weeks of onset. The CSF formula typically shows a lymphocytic pleocytosis, and low glucose and high protein concentrations...
March 2017: Microbiology Spectrum
https://www.readbyqxmd.com/read/28262051/hand-washing
#17
Erin Dean
Essential facts Antimicrobial resistance develops when the medicines are used inappropriately. Global estimates suggest that every year more than 700,000 people die from drug-resistant strains of common bacterial and viral infections, such as the human immunodeficiency virus, tuberculosis and malaria. If antimicrobial resistance continues to increase, this number could rise to ten million a year by 2050.
March 6, 2017: Nursing Children and Young People
https://www.readbyqxmd.com/read/28180188/imidazoles-induce-reactive-oxygen-species-in-mycobacterium-tuberculosis-which-is-not-associated-with-cell-death
#18
Heather A Howell Wescott, David M Roberts, Christian L Allebach, Rachel Kokoczka, Tanya Parish
Azoles are a class of antimicrobial drugs used clinically to treat yeast and fungal infections. Against pathogenic yeast and fungi, azoles act by inhibiting the activity of the cytochrome P450 Cyp51, which is involved in the synthesis of a critical component of the yeast and fungal cell membrane. Azoles have antibacterial activity, including against mycobacteria, but the basis for this activity is not well-understood. We demonstrated that imidazoles are bactericidal to Mycobacterium tuberculosis. A marked increase in reactive oxygen species (ROS) was observed within imidazole-treated M...
January 31, 2017: ACS Omega
https://www.readbyqxmd.com/read/28174307/a-bioengineered-three-dimensional-cell-culture-platform-integrated-with-microfluidics-to-address-antimicrobial-resistance-in-tuberculosis
#19
Magdalena K Bielecka, Liku B Tezera, Robert Zmijan, Francis Drobniewski, Xunli Zhang, Suwan Jayasinghe, Paul Elkington
Antimicrobial resistance presents one of the most significant threats to human health, with the emergence of totally drug-resistant organisms. We have combined bioengineering, genetically modified bacteria, longitudinal readouts, and fluidics to develop a transformative platform to address the drug development bottleneck, utilizing Mycobacterium tuberculosis as the model organism. We generated microspheres incorporating virulent reporter bacilli, primary human cells, and an extracellular matrix by using bioelectrospray methodology...
February 7, 2017: MBio
https://www.readbyqxmd.com/read/28167588/prevalence-of-staphylococcus-aureus-nasal-carriage-in-human-immunodeficiency-virus-infected-and-uninfected-children-in-botswana-prevalence-and-risk-factors
#20
Michael J A Reid, Rebecca S B Fischer, Naledi Mannathoko, Charles Muthoga, Erin McHugh, Heather Essigmann, Eric L Brown, Andrew P Steenhoff
AbstractStaphylococcus aureus is an important cause of morbidity and mortality in children in sub-Saharan Africa (SSA). A major risk factor for staphylococcal infection is S. aureus colonization of the anterior nares. We sought to define risk factors for S. aureus carriage and characterize antimicrobial resistance patterns in children in Botswana. A cross-sectional study was conducted at two clinical sites in southern Botswana. Patients under 18 years of age underwent two nasal swabs and brief interviews, 4 weeks apart...
April 2017: American Journal of Tropical Medicine and Hygiene
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