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https://www.readbyqxmd.com/read/28542279/oligopeptides-as-full-length-new-delhi-metallo-%C3%AE-lactamase-1-ndm-1-inhibitors
#1
Bingzheng Shen, Chengliang Zhu, Xiang Gao, Gang Liu, Jinchun Song, Yan Yu
'Superbug' bacteria producing NDM-1 enzyme causing wide public concern were first detected in a patient who visited India in 2008. It's an effective approach to combining β-lactam antibiotics with NDM-1 inhibitor for treating NDM-1 producing strain infection. In our research, we designed ten oligopeptides, tested IC50 values against NDM-1 enzyme, determined the MIC values of synergistic antibacterial effect and explored the binding model. We found that the oligopeptides 2 (Cys-Phe) and 5 (Cys-Asp) respectively presented IC50 values of 113 μM and 68 μM and also displayed favorable synergistic effects of the inhibitors in combination with ertapenem against genetic engineering-host E...
2017: PloS One
https://www.readbyqxmd.com/read/28526792/environmental-spread-of-ndm-1-producing-multi-drug-resistant-bacteria-in-dhaka-bangladesh
#2
Mohammad Aminul Islam, Moydul Islam, Rashedul Hasan, M Iqbal Hossain, Ashikun Nabi, Mahdia Rahman, Wil H F Goessens, Hubert P Endtz, Alexandria B Boehm, Shah M Faruque
Resistance to carbapenem antibiotics through the production of New Delhi Metallo-β-lactamase-1 (NDM-1) constitutes an emerging challenge in the treatment of bacterial infections. To monitor possible source of spread of these organisms in Dhaka, Bangladesh, we conducted comparative analysis of waste water samples from hospital adjacent areas (HAR) and from community areas (COM) as well as public tap water samples for the occurrence and characteristics of NDM-1 producing bacteria. Of 72 HAR samples tested 51 (71%) were positive for NDM-1-producing bacteria as evidenced by phenotypic tests and the presence of blaNDM-1 gene, compared to 5 of 41 (12...
May 19, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28515215/an-outbreak-of-ndm-1-producing-klebsiella-pneumoniae-in-a-dutch-hospital-with-interspecies-transfer-of-the-resistance-plasmid-and-unexpected-occurrence-in-unrelated-healthcare-centers
#3
Thijs Bosch, Suzanne P M Lutgens, Mirjam H A Hermans, Peter C Wever, Peter M Schneeberger, Nicole H M Renders, Alexander C A P Leenders, Jan A J W Kluytmans, Annelot Schoffelen, Daan Notermans, Sandra Witteveen, Erik Bathoorn, Leo M Schouls
Introduction. In the Netherlands, the number of cases with New Delhi metallo-beta-lactamase (NDM)-positive Enterobacteriaceae is low. Here, we report an outbreak of NDM-1 producing Klebsiella pneumoniae in a Dutch hospital with interspecies transfer of the resistance plasmid and unexpected occurrence in other unrelated healthcare centers (HCCs).Methods. Next-generation sequencing was performed on 250 carbapenemase-producing Enterobacteriaceae isolates including 42 NDM-positive isolates obtained from 29 persons at the outbreak site...
May 17, 2017: Journal of Clinical Microbiology
https://www.readbyqxmd.com/read/28512093/population-genomic-analysis-of-1-777-extended-spectrum-beta-lactamase-producing-klebsiella-pneumoniae-isolates-houston-texas-unexpected-abundance-of-clonal-group-307
#4
S Wesley Long, Randall J Olsen, Todd N Eagar, Stephen B Beres, Picheng Zhao, James J Davis, Thomas Brettin, Fangfang Xia, James M Musser
Klebsiella pneumoniae is a major human pathogen responsible for high morbidity and mortality rates. The emergence and spread of strains resistant to multiple antimicrobial agents and documented large nosocomial outbreaks are especially concerning. To develop new therapeutic strategies for K. pneumoniae, it is imperative to understand the population genomic structure of strains causing human infections. To address this knowledge gap, we sequenced the genomes of 1,777 extended-spectrum beta-lactamase-producing K...
May 16, 2017: MBio
https://www.readbyqxmd.com/read/28506721/first-report-of-ndm-1-producing-clinical-isolate-of-leclercia-adecarboxylata-in-spain
#5
Cristina Riazzo, Lorena López-Cerero, María Dolores Rojo-Martín, Yannick Hoyos-Mallecot, Felipe Fernández-Cuenca, Jose Luis Martín-Ruíz, Álvaro Pascual-Hernández, Thierry Naas, Jose María Navarro-Marí
We describe the case of NDM-1-producing Leclercia adecarboxylata recovered from the clinical sample of a patient hospitalized for a trauma-related injury to his foot. The isolate was resistant to all beta-lactams, quinolones, trimetroprim-sulfametoxazol, gentamicin and tobramicyn. The blaNDM-1 gene was located in a conjugative plasmid that also contained the blaSHV-12 gene and was preceded by a disrupted insertion sequence of ISAba125. The plasmid belongs to the incompatibility group X3, which is known to be an important vector for NDM-1 dissemination in China...
May 3, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/28505394/1-2-4-triazole-3-thione-compounds-as-inhibitors-of-di-zinc-metallo-%C3%AE-lactamases
#6
Laurent Sevaille, Laurent Gavara, Carine Bebrone, Filomena De Luca, Lionel Nauton, Maud Achard, Paola Mercuri, Silvia Tanfoni, Luisa Borgianni, Carole Guyon, Pauline Lonjon, Gülhan Turan-Zitouni, Julia Dzieciolowski, Katja Becker, Lionel Bénard, Ciaran Condon, Ludovic Maillard, Jean Martinez, Jean-Marie Frère, Otto Dideberg, Moreno Galleni, Jean-Denis Docquier, Jean-François Hernandez
Metallo-β-lactamases (MBL) cause resistance of Gram-negative bacteria to β-lactam antibiotics and are of serious concern because they can inactivate the last-resort carbapenems and because MBL inhibitors of clinical value are still lacking. We have previously identified the original binding mode of a 4-amino-1,2,4-triazole-3-thione compound, IIIA, within the di-zinc active site of the L1 MBL. Here, we present the crystallographic structure of a complex of L1 with the corresponding non-amino compound IIIB...
May 15, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28505330/acinetobacter-baumannii-transfers-the-blandm-1-gene-via-outer-membrane-vesicles
#7
Somdatta Chatterjee, Ayan Mondal, Shravani Mitra, Sulagna Basu
Objectives: To investigate the transmission of the gene encoding New Delhi metallo-β-lactamase-1 ( bla NDM-1 ) through outer membrane vesicles (OMVs) released from an Acinetobacter baumannii strain (A_115). Methods: Isolation and purification of OMVs by density gradient from a carbapenem-resistant clinical strain of A. baumannii harbouring plasmid-mediated bla NDM-1 and aac(6')-Ib-cr genes was performed. DNA was purified from the OMVs and used for PCR and dot-blot analysis...
May 12, 2017: Journal of Antimicrobial Chemotherapy
https://www.readbyqxmd.com/read/28490008/an-uncommon-st1224-ndm-1-producing-klebsiella-pneumoniae-isolated-from-the-bloodstream-of-a-leukemia-patient-in-china
#8
Xiaoxiao Zhang, Jia Du, Cui Zhou, Jianming Cao, Hong Lu, Haiyang Liu, Wenzi Bi, Tieli Zhou
AIMS: This study aimed to analyze the clinical data and characteristics of an NDM-1 (New Delhi metallo-β-lactamase-1)-producing Klebsiella pneumoniae isolated from the bloodstream of a leukemia patient. MATERIALS AND METHODS: A retrospective analysis was used for the clinical data of the patient. The modified Hodge test (MHT) and ethylenediaminetetraacetic acid (EDTA)-disk synergy test were used for detecting metallo-β-lactamase. Antibiotic resistance was determined using the agar dilution method...
May 11, 2017: Chemotherapy
https://www.readbyqxmd.com/read/28489087/hydrolysis-of-cephalexin-and-meropenem-by-new-delhi-metallo-%C3%AE-lactamase-the-substrate-protonation-mechanism-is-drug-dependent
#9
Chandan Kumar Das, Nisanth N Nair
Emergence of antibiotic resistance due to New Delhi metallo-β-lactamase (NDM-1) bacterial enzymes is of great concern due to their ability to hydrolyze a wide range of antibiotics. There are ongoing efforts to obtain the atomistic details of the hydrolysis mechanism in order to develop inhibitors for NDM-1. In particular, it remains elusive how drug molecules of different families of antibiotics are hydrolyzed by NDM-1 in an efficient manner. Here we report the detailed molecular mechanism of NDM-1 catalyzed hydrolysis of cephalexin, a cephalosporin family drug, and meropenem, a carbapenem family drug...
May 24, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28487071/diversity-oriented-sustainable-synthesis-of-antimicrobial-spiropyrrolidine-thiapyrrolizidine-oxindole-derivatives-new-ligands-for-a-metallo-%C3%AE-lactamase-from-klebsiella-pneumonia
#10
Anshu Dandia, Shahnawaz Khan, Pragya Soni, Aayushi Indora, Dinesh Kumar Mahawar, Prateek Pandya, Chetan Singh Chauhan
A simple, environmentally benign and highly proficient microwave assisted one-pot approach for the synthesis of antimicrobial spiropyrrolidine/thiapyrrolizidine oxindole derivatives is reported assembling two pharmacophoric moieties (1,3-indanedione and pyrrolidine/thiapyrrolizidine) in a single molecular framework via three-component 1,3-dipolar cycloaddition reaction of substituted isatin, sarcosine/1,3-thiazoles-4-carboxylic acid and Knoevenagel adduct (2-Cyano-3-phenyl-acrylic acid ethyl ester or 2-Benzylidene-malononitrile) in 2,2,2-trifluoroethanol as a reusable green solvent...
April 27, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28486840/molecular-characterization-of-carbapenem-resistant-enterobacteriaceae-yields-increasing-rates-of-ndm-1-carbapenemases-and-colistin-resistance-in-an-oxa-48-endemic-area
#11
Zeynep Cizmeci, Elif Aktas, Baris Otlu, Ozlem Acikgoz, Seyhan Ordekci
We aimed to characterize carbapenem-resistant isolates in a tertiary hospital in Istanbul, Turkey, high-prevelance area for OXA-48 producers. About 76 Enterobacteriaceae clinical isolates were included. Carbapenemase production was detected by Carbapenem Inactivation Method and carbapenemase genes were investigated by PCR. The clonal relationships were evaluated by AP-PCR. Nineteen Klebsiella pneumoniae isolates were colistin resistant. About 75 isolates yielded carbapenemase by CIM. 52 OXA-48, 17 NDM-1 and 2 VIM-5 carbapenemase genes were detected...
May 9, 2017: Journal of Chemotherapy
https://www.readbyqxmd.com/read/28473912/high-burden-of-carbapenem-resistant-enterobacteriaceae-cre-fecal-carriage-at-a-teaching-hospital-cost-effectiveness-of-screening-in-low-resource-setting
#12
Abdul Rahman Zaidah, Nurul Izzah Mohammad, Siti Suraiya, Azian Harun
BACKGROUND: Infections by multidrug-resistant gram-negative bacteria (MDR-GNB) have been continuously growing and pose challenge to health institution globally. Carbapenem-resistant Enterobacteriacea (CRE) was identified as one of the MDR-GNB which has limited treatment options and higher mortality compared to those of sensitive strains. We report an increased burden of CRE fecal carriage at a hospital in the North-eastern region of Malaysia. METHODS: A retrospective descriptive study from August 2013 to December 2015 was conducted in the Medical Microbiology & Parasitology laboratory of Hospital Universiti Sains Malaysia, which is a tertiary teaching hospital with more than 700 beds...
2017: Antimicrobial Resistance and Infection Control
https://www.readbyqxmd.com/read/28454673/synthesis-of-octapeptin-c4-and-biological-profiling-against-ndm-1-and-polymyxin-resistant-bacteria
#13
Bernd Becker, Mark S Butler, Karl A Hansford, Alejandra Gallardo-Godoy, Alysha G Elliott, Johnny X Huang, David J Edwards, Mark A T Blaskovich, Matthew A Cooper
The first synthesis of octapeptin C4 was achieved using a combination of solid phase synthesis and off-resin cyclisation. Octapeptin C4 displayed antibiotic activity against multi-drug resistant, NDM-1 and polymyxin-resistant Gram-negative bacteria, with moderate activity against Staphylococcus aureus. The linear analogue of octapeptin C4 was also prepared, which showed reduced activity.
June 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28450501/draft-genome-sequence-of-ndm-1-producing-leclercia-adecarboxylata
#14
Yannick Hoyos-Mallecot, María Dolores Rojo-Martín, Rémy A Bonnin, Elodie Creton, Jose María Navarro Marí, Thierry Naas
Here, we provide the first draft genome sequence of NDM-1-producing Leclercia adecarboxylata, a human-opportunistic pathogen. The draft genome sequence consists of a total length of 5.13 Mbp, with an average G+C content of 55.2%.
April 27, 2017: Genome Announcements
https://www.readbyqxmd.com/read/28449650/structure-genetics-and-worldwide-spread-of-new-delhi-metallo-%C3%AE-lactamase-ndm-a-threat-to-public-health
#15
REVIEW
Asad U Khan, Lubna Maryam, Raffaele Zarrilli
BACKGROUND: The emergence of carbapenemase producing bacteria, especially New Delhi metallo-β-lactamase (NDM-1) and its variants, worldwide, has raised amajor public health concern. NDM-1 hydrolyzes a wide range of β-lactam antibiotics, including carbapenems, which are the last resort of antibiotics for the treatment of infections caused by resistant strain of bacteria. MAIN BODY: In this review, we have discussed bla NDM-1variants, its genetic analysis including type of specific mutation, origin of country and spread among several type of bacterial species...
April 27, 2017: BMC Microbiology
https://www.readbyqxmd.com/read/28445786/metallo-%C3%AE-lactamase-inhibitors-by-bioisosteric-replacement-preparation-activity-and-binding
#16
Susann Skagseth, Sundus Akhter, Marianne H Paulsen, Zeeshan Muhammad, Silje Lauksund, Ørjan Samuelsen, Hanna-Kirsti S Leiros, Annette Bayer
Bacterial resistance is compromising the use of β-lactam antibiotics including carbapenems. The main resistance mechanism against β-lactams is hydrolysis of the β-lactam ring mediated by serine- or metallo-β-lactamases (MBLs). Although several inhibitors of MBLs have been reported, none has been developed into a clinically useful inhibitor. Mercaptocarboxylic acids are among the most prominent scaffolds reported as MBL inhibitors. In this study, the carboxylate group of mercaptocarboxylic acids was replaced with bioisosteric groups like phosphonate esters, phosphonic acids and NH-tetrazoles...
April 14, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28437228/first-case-of-ndm-1-producing-klebsiella-pneumoniae-in-annaba-university-hospital-algeria
#17
Amel Abderrahim, Nassima Djahmi, Charlotte Pujol, Sabina Nedjai, Mohamed Cherif Bentakouk, Djamila Kirane-Gacemi, Mazouz Dekhil, Albert Sotto, Jean-Philippe Lavigne, Alix Pantel
AIM: The aim of this study was to characterize two carbapenem-resistant Klebsiella pneumoniae isolates recovered from urine samples in a patient hospitalized at Annaba University hospital (Algeria) in 2014. RESULTS: Two K. pneumoniae isolates were studied because they proved resistant to almost all antibiotics tested with a high level resistance to ertapenem (minimum inhibitory concentration = 32 mg/L). The results of modified Hodge test and combined disk test (ROSCO Diagnostica, Taastrup, Denmark) were positive...
February 22, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28432959/molecular-dynamics-simulation-studies-of-novel-%C3%AE-lactamase-inhibitor
#18
Farhan Ul Haq, Asma Abro, Saad Raza, Klaus R Liedl, Syed Sikander Azam
New Delhi Metallo-β-Lactamase-1 (NDM-1) has drawn great attention due to its diverse antibiotic resistant activity. It can hydrolyze almost all clinically available β-lactam antibiotics. To inhibit the activity of NDM-1 a new strategy is proposed using computational methods. Molecular dynamics (MD) simulations are used to analyze the molecular interactions between selected inhibitor candidates and NDM-1 structure. The enzyme-ligand complex is subject to binding free energy calculations using MM(PB/GB)SA methods...
April 4, 2017: Journal of Molecular Graphics & Modelling
https://www.readbyqxmd.com/read/28411227/fate-and-persistence-of-a-pathogenic-ndm-1-positive-escherichia-coli-strain-in-anaerobic-and-aerobic-sludge-microcosms
#19
David Mantilla-Calderon, Pei-Ying Hong
The presence of emerging biological pollutants in treated wastewater effluents has gained attention due to increased interest in water reuse. To evaluate the effectiveness of the removal of such contaminants by the conventional wastewater treatment process, the fate and decay kinetics of NDM-1-positive Escherichia coli strain PI7 and its plasmid-encoded antibiotic resistance genes (ARGs) were assessed in microcosms of anaerobic and aerobic sludge. Results showed that E. coli PI7 decayed at a significantly slower rate under anaerobic conditions...
April 14, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28404680/development-and-validation-of-a-lateral-flow-immunoassay-for-the-rapid-detection-of-ndm-producing-enterobacteriaceae
#20
Hervé Boutal, Thierry Naas, Karine Devilliers, Saoussen Oueslati, Laurent Dortet, Sandrine Bernabeu, Stéphanie Simon, Hervé Volland
The global spread of carbapenemase-producing Enterobacteriaceae (CPE) that are often resistant to most, if not all, classes of antibiotics is a major public health concern. NDM-1 carbapenemase is among the most worrisome carbapenemases given its rapid worldwide spread. We have developed and evaluated a lateral flow immunoassay (LFIA, called NDM LFIA) for rapid and reliable detection of NDM-like carbapenemase-producing Enterobacteriaceae from culture colonies.We evaluated the NDM LFIA using 175 reference enterobacterial isolates with characterized ß-lactamase gene content and 74 non-duplicate consecutive carbapenem-resistant clinical isolates referred for expertise to the French National Reference Center (NRC) for antibiotic resistance during a one-week period (in June 2016)...
April 12, 2017: Journal of Clinical Microbiology
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