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https://www.readbyqxmd.com/read/28928474/using-experimental-evolution-to-identify-druggable-targets-that-could-inhibit-the-evolution-of-antimicrobial-resistance
#1
Heer H Mehta, Amy G Prater, Yousif Shamoo
With multi-drug and pan-drug-resistant bacteria becoming increasingly common in hospitals, antibiotic resistance has threatened to return us to a pre-antibiotic era that would completely undermine modern medicine. There is an urgent need to develop new antibiotics and strategies to combat resistance that are substantially different from earlier drug discovery efforts. One such strategy that would complement current and future antibiotics would be a class of co-drugs that target the evolution of resistance and thereby extend the efficacy of specific classes of antibiotics...
September 20, 2017: Journal of Antibiotics
https://www.readbyqxmd.com/read/28892368/structure-based-design-and-synthesis-of-apramycin-paromomycin-analogues-importance-of-the-configuration-at-the-6-position-and-differences-between-the-6-amino-and-hydroxy-series
#2
Appi Reddy Mandhapati, Guanyu Yang, Takayuki Kato, Dimitri Shcherbakov, Sven N Hobbie, Andrea Vasella, Erik C Böttger, David Crich
The preparation of a series of four analogues of the aminoglycoside antibiotics neomycin and paromomycin is described in which ring I, involved in critical binding interactions with the ribosomal target, is replaced by an apramycin-like dioxabicyclo[4.4.0]octane system. The effect of this modification is to lock the hydroxymethyl side chain of the neomycin or paromomycin ring I, as part of dioxabicyclooctane ring, into either the gauche-gauche or the gauche-trans conformation (respectively axial or equatorial to the bicyclic system)...
September 11, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/28886999/advances-in-macrocyclic-peptide-based-antibiotics
#3
Anatol Luther, Christian Bisang, Daniel Obrecht
Macrocyclic peptide-based natural products have provided powerful new antibiotic drugs, drug candidates, and scaffolds for medicinal chemists as a source of inspiration to design novel antibiotics. While most of those natural products are active mainly against Gram-positive pathogens, novel macrocyclic peptide-based compounds have recently been described, which exhibit potent and specific activity against some of the most problematic Gram-negative ESKAPE pathogens. This mini-review gives an up-date on recent developments...
August 19, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28861082/polyvinylpyrrolidone-capped-silver-nanoparticle-inhibits-infection-of-carbapenem-resistant-strain-of-acinetobacter-baumannii-in-the-human-pulmonary-epithelial-cell
#4
Vishvanath Tiwari, Monalisa Tiwari, Vandana Solanki
Acinetobacter baumannii, an opportunistic ESKAPE pathogen, causes respiratory and urinary tract infections. Its prevalence increases gradually in the clinical setup. Pathogenicity of Acinetobacter is significantly influenced by its ability to infect and survive in human pulmonary cells. Therefore, it is important to study the infection of A. baumannii in human pulmonary host cell (A-549), monitoring surface interacting and internalized bacteria. It was found that during infection of A. baumannii, about 40% bacteria adhered to A-549, whereas 20% got internalized inside pulmonary cell and induces threefold increase in the reactive oxygen species production...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28774148/synthesis-and-structural-characterization-of-silver-nanoparticles-stabilized-with-3-mercapto-1-propansulfonate-and-1-thioglucose-mixed-thiols-for-antibacterial-applications
#5
Francesco Porcaro, Laura Carlini, Andrea Ugolini, Daniela Visaggio, Paolo Visca, Ilaria Fratoddi, Iole Venditti, Carlo Meneghini, Laura Simonelli, Carlo Marini, Wojciech Olszewski, Nitya Ramanan, Igor Luisetto, Chiara Battocchio
The synthesis, characterization and assessment of the antibacterial properties of hydrophilic silver nanoparticles (AgNPs) were investigated with the aim to probe their suitability for innovative applications in the field of nanobiotechnology. First, silver nanoparticles were synthetized and functionalized with two capping agents, namely 3-mercapto-1-propansulfonate (3MPS) and 1-β-thio-d-glucose (TG). The investigation of the structural and electronic properties of the nano-systems was carried out by means of X-ray Photoelectron Spectroscopy (XPS) and X-ray Absorption Spectroscopy (XAS)...
December 20, 2016: Materials
https://www.readbyqxmd.com/read/28743946/identification-of-the-eskape-pathogens-by-mass-spectrometric-analysis-of-microbial-membrane-glycolipids
#6
Lisa M Leung, William E Fondrie, Yohei Doi, J Kristie Johnson, Dudley K Strickland, Robert K Ernst, David R Goodlett
Rapid diagnostics that enable identification of infectious agents improve patient outcomes, antimicrobial stewardship, and length of hospital stay. Current methods for pathogen detection in the clinical laboratory include biological culture, nucleic acid amplification, ribosomal protein characterization, and genome sequencing. Pathogen identification from single colonies by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) analysis of high abundance proteins is gaining popularity in clinical laboratories...
July 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28712104/do-bacteria-isolated-from-icu-patients-eskape-antibiotic-treatment-in-vitro-susceptibility-of-the-enterobacteriaceae-family-to-tigecycline
#7
Katarzyna Talaga-Ćwiertnia, Paweł Krzyściak, Małgorzata Bulanda
BACKGROUND: Enterobacteriaceae are currently causing the majority of healthcare-associated infections (HAI) and simultaneously expressing increasing levels of antibiotic resistance. The purpose of this study is to assess the in vitro sensitivity of MDR strains from the family Enterobacteriaceae to tigecycline in relation to their origin from patients hospitalized in intensive care units (ICUs) and non-ICUs. METHODS: The study involved 156 clinically significant strains of the Enterobacteriaceae family isolated from patients with complicated intraabdominal infections (cIAIs) and/or complicated skin and skin structure infections (cSSSIs) hospitalized in ICUs and other surgical departments...
2017: Anaesthesiology Intensive Therapy
https://www.readbyqxmd.com/read/28710611/bad-bacteria-in-acute-appendicitis-rare-but-relevant
#8
Alexander Reinisch, Patrizia Malkomes, Nils Habbe, Wolf Otto Bechstein, Juliane Liese
PURPOSE: Bacterial infections are a factor for morbidity in patients with acute appendicitis (AA). The spreading of multidrug-resistant (MDR) bacteria is a significant problem in surgery, and the most relevant MDR pathogens are summarized as Enterobacteriaceae, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococci (ESKAPE) bacteria. Data regarding the species and distribution of bacteria in AA are available, but information about the resistances and their relevance is deficient...
July 15, 2017: International Journal of Colorectal Disease
https://www.readbyqxmd.com/read/28675109/titanium-surfaces-immobilized-with-the-major-antimicrobial-fragment-fk-16-of-human-cathelicidin-ll-37-are-potent-against-multiple-antibiotic-resistant-bacteria
#9
Biswajit Mishra, Guangshun Wang
Infections on implanted medical devices are a challenging problem, especially when bacteria form difficult-to-treat biofilms. Antimicrobial peptides are considered to be a solution due to their potency against antibiotic-resistant superbugs. Previously, the authors' laboratory demonstrated the prevention of staphylococcal biofilm formation in an animal catheter model by injecting merecidin (formerly known as 17BIPHE2), a peptide engineered based on the only human cathelicidin. This study documents an alternative solution via covalent immobilization of FK-16, amino acid sequence FKRIVQRIKDFLRNLV-amide, which corresponds to the major antimicrobial region (residues 17-32) of LL-37...
August 2017: Biofouling
https://www.readbyqxmd.com/read/28642945/nonribosomal-peptide-synthetase-biosynthetic-clusters-of-eskape-pathogens
#10
REVIEW
Andrew M Gulick
Covering: up to 2017.Natural products are important secondary metabolites produced by bacterial and fungal species that play important roles in cellular growth and signaling, nutrient acquisition, intra- and interspecies communication, and virulence. A subset of natural products is produced by nonribosomal peptide synthetases (NRPSs), a family of large, modular enzymes that function in an assembly line fashion. Because of the pharmaceutical activity of many NRPS products, much effort has gone into the exploration of their biosynthetic pathways and the diverse products they make...
August 2, 2017: Natural Product Reports
https://www.readbyqxmd.com/read/28641558/bis-2-aminoimidazolines-and-bisguanidines-synthetic-approaches-antiparasitic-activity-and-dna-binding-properties
#11
Christophe Dardonville, J Jonathan Nué Martínez
BACKGROUND: Parasitic diseases caused by protozoan parasites of the genus Trypanosoma and Plasmodium cause some of the deadliest and disabling human infections in tropical and subtropical areas. Diphenyl-based bis(2-phenylimino)imidazolidines and bisguanidines are extremely potent antiparasitic agents against Trypanosoma brucei (etiological agent of African trypanosomiasis) and Plasmodium falciparum (etiological agent of severe malaria). Many of these compounds are also curative in mouse models of stage 1 African trypanosomiasis representing promising leads for the development of antitrypanosomal drugs...
June 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28630188/identification-of-1-2-4-dichlorophenethyl-amino-3-phenoxypropan-2-ol-a-novel-antibacterial-compound-active-against-persisters-of-pseudomonas-aeruginosa
#12
Veerle Liebens, Valerie Defraine, Wouter Knapen, Toon Swings, Serge Beullens, Romu Corbau, Arnaud Marchand, Patrick Chaltin, Maarten Fauvart, Jan Michiels
Antibiotics typically fail to completely eradicate a bacterial population, leaving a small fraction of transiently antibiotic-tolerant persister cells intact. Persisters are therefore seen to be a major cause of treatment failure and greatly contribute to the recalcitrant nature of chronic infections. The current study focused on Pseudomonas aeruginosa, a Gram-negative pathogen belonging to the notorious ESKAPE group of pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) and, due to increasing resistance against most conventional antibiotics, posing a serious threat to human health...
September 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28603227/patterns-of-multi-drug-resistant-bacteria-at-first-culture-from-patients-admitted-to-a-third-level-university-hospital-in-calabria-from-2011-to-2014-implications-for-empirical-therapy-and-infection-control
#13
Mariaconcetta Reale, Alessio Strazzulla, Angela Quirino, Claudia Rizzo, Vito Marano, Maria Concetta Postorino, Maria Mazzitelli, Giuseppe Greco, Vincenzo Pisani, Chiara Costa, Bruno Mario Cesana, Maria Carla Liberto, Carlo Torti, Alfredo Focà
Surveillance of antimicrobial drug resistance is fundamental to guide empirical treatment. However, the European Antimicrobial Resistance Surveillance Network provides a general picture, which might not be applicable to clinical settings that are excluded from this survey. We evaluated resistance patterns of ESKAPE isolates over a four-year period in a third level University hospital in the province of Catanzaro (Southern Italy). In this retrospective study, we evaluated the frequency of ESKAPE isolates with different resistance patterns (group 1=low-resistant bacteria; group 2=multi-drug and extremely drug-resistant bacteria; group 3=pan-resistant bacteria), stratified by year (2011, 2012, 2013 and 2014), hospital units (intensive care units, medical and surgical units) and by sample type (urine, blood, wound swabs, respiratory samples, other samples)...
June 1, 2017: Le Infezioni in Medicina
https://www.readbyqxmd.com/read/28533769/celecoxib-enhances-the-efficacy-of-low-dose-antibiotic-treatment-against-polymicrobial-sepsis-in-mice-and-clinical-isolates-of-eskape-pathogens
#14
Madhavi Annamanedi, Gajapati Y N Varma, K Anuradha, Arunasree M Kalle
Treatment of multidrug resistant bacterial infections has been a great challenge globally. Previous studies including our study have highlighted the use of celecoxib, a non-steroidal anti-inflammatory drug in combination with antibiotic has decreased the minimal inhibitory concentration to limit Staphylococcus aureus infection. However, the efficacy of this combinatorial treatment against various pathogenic bacteria is not determined. Therefore, we have evaluated the potential use of celecoxib in combination with low doses of antibiotic in limiting Gram-positive and Gram-negative bacteria in vivo in murine polymicrobial sepsis developed by cecum ligation and puncture (CLP) method and against clinically isolated human ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28458799/the-use-of-bloodstream-infection-mortality-to-measure-the-impact-of-antimicrobial-stewardship-interventions-assessing-the-evidence
#15
REVIEW
Sonali Coulter, Jason A Roberts, Krispin Hajkowicz, Kate Halton
This review sets out to evaluate the current evidence on the impact of inappropriate therapy on bloodstream infections (BSI) and associated mortality. Based on the premise that better prescribing practices should result in better patient outcomes, BSI mortality may be a useful metric to evaluate antimicrobial stewardship (AMS) interventions. A systematic search was performed in key medical databases to identify papers published in English between 2005 and 2015 that examined the association between inappropriate prescribing and BSI mortality in adult patients...
March 30, 2017: Infectious Disease Reports
https://www.readbyqxmd.com/read/28448954/copper-complexes-containing-thiosemicarbazones-derived-from-6-nitropiperonal-antimicrobial-and-biophysical-properties
#16
Floyd A Beckford, Kelsey R Webb
A series of four thiosemicarbazones from 6-nitropiperonal along with the corresponding copper complexes were synthesized. The biophysical characteristics of the complexes were investigated by the binding to DNA and human serum albumin. The binding to DNA is moderate; the binding constants run from (0.49-7.50)×10(4)M(-1). In relation to HSA, the complexes interact strongly with binding constants on the order of 10(5)M(-1). The complexes also display antioxidant behavior as determined by the ability to scavenge diphenylpicrylhydrazyl (dpph) and nitric oxide radicals...
April 20, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28399424/resistance-among-gram-negative-eskape-pathogens-isolated-from-hospitalized-patients-with-intra-abdominal-and-urinary-tract-infections-in-latin-american-countries-smart-2013-2015
#17
James A Karlowsky, Daryl J Hoban, Meredith A Hackel, Sibylle H Lob, Daniel F Sahm
Gram-negative ESKAPE pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) are important etiologic agents of nosocomial infection that are frequently resistant to broad-spectrum antimicrobial agents. Gram-negative ESKAPE pathogens were collected from hospitalized patients in 11 Latin American countries from 2013 to 2015 as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART) global surveillance program. In total, 2113 isolates from intra-abdominal infections (IAI) and 970 isolates from urinary tract infections (UTI) were tested against antimicrobial agents using standardized CLSI broth microdilution methodology...
May 2017: Brazilian Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28373195/structural-modification-of-lipopolysaccharide-conferred-by-mcr-1-in-gram-negative-eskape-pathogens
#18
Yi-Yun Liu, Courtney E Chandler, Lisa M Leung, Christi L McElheny, Roberta T Mettus, Robert M Q Shanks, Jian-Hua Liu, David R Goodlett, Robert K Ernst, Yohei Doi
mcr-1 was initially reported as the first plasmid-mediated colistin resistance gene in clinical isolates of Escherichia coli and Klebsiella pneumoniae in China and has subsequently been identified worldwide in various species of the family Enterobacteriaceaemcr-1 encodes a phosphoethanolamine transferase, and its expression has been shown to generate phosphoethanolamine-modified bis-phosphorylated hexa-acylated lipid A in E. coli Here, we investigated the effects of mcr-1 on colistin susceptibility and on lipopolysaccharide structures in laboratory and clinical strains of the Gram-negative ESKAPE (Enterococcus faecium, Staphylococcus aureus, K...
June 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28343384/n6-n6-and-o4-modifications-to-neomycin-affect-ribosomal-selectivity-without-compromising-antibacterial-activity
#19
Girish C Sati, Dimitri Shcherbakov, Sven N Hobbie, Andrea Vasella, Erik C Böttger, David Crich
The synthesis of a series of neomycin derivatives carrying the 2-hydroxyethyl substituent on N6' and/or N6‴ both alone and in combination with a 4'-O-ethyl group is described. By means of cell-free translation assays with wild-type bacterial ribosomes and their hybrids with eukaryotic decoding A sites, we investigate how individual substituents and their combinations affect activity and selectivity at the target level. In principle, and as shown by cell-free translation assays, modifications of the N6' and N6‴ positions allow enhancement of target selectivity without compromising antibacterial activity...
May 12, 2017: ACS Infectious Diseases
https://www.readbyqxmd.com/read/28335205/photosensitizer-embedded-polyacrylonitrile-nanofibers-as-antimicrobial-non-woven-textile
#20
Sarah L Stanley, Frank Scholle, Jiadeng Zhu, Yao Lu, Xiangwu Zhang, Xingci Situ, Reza A Ghiladi
Toward the objective of developing platform technologies for anti-infective materials based upon photodynamic inactivation, we employed electrospinning to prepare a non-woven textile comprised of polyacrylonitrile nanofibers embedded with a porphyrin-based cationic photosensitizer; termed PAN-Por((+)). Photosensitizer loading was determined to be 34.8 nmol/mg material; with thermostability to 300 °C. Antibacterial efficacy was evaluated against four bacteria belonging to the ESKAPE family of pathogens (Staphylococcus aureus; vancomycin-resistant Enterococcus faecium; Acinetobacter baumannii; and Klebsiella pneumonia), as well as Escherichia coli...
April 20, 2016: Nanomaterials
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