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https://www.readbyqxmd.com/read/28912448/a-general-reaction-mechanism-for-carbapenem-hydrolysis-by-mononuclear-and-binuclear-metallo-%C3%AE-lactamases
#1
María-Natalia Lisa, Antonela R Palacios, Mahesh Aitha, Mariano M González, Diego M Moreno, Michael W Crowder, Robert A Bonomo, James Spencer, David L Tierney, Leticia I Llarrull, Alejandro J Vila
Carbapenem-resistant Enterobacteriaceae threaten human health, since carbapenems are last resort drugs for infections by such organisms. Metallo-β-lactamases (MβLs) are the main mechanism of resistance against carbapenems. Clinically approved inhibitors of MBLs are currently unavailable as design has been limited by the incomplete knowledge of their mechanism. Here, we report a biochemical and biophysical study of carbapenem hydrolysis by the B1 enzymes NDM-1 and BcII in the bi-Zn(II) form, the mono-Zn(II) B2 Sfh-I and the mono-Zn(II) B3 GOB-18...
September 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28878746/inhibition-of-new-delhi-metallo-%C3%AE-lactamase-1-ndm-1-producing-escherichia-coli-ir-6-by-selected-plant-extracts-and-their-synergistic-actions-with-antibiotics
#2
Brinda Chandar, Sundar Poovitha, Kaliappan Ilango, Ramasamy MohanKumar, Madasamy Parani
Improper use of antibiotics has led to a great concern in the development of pathogenic microbial resistance. New Delhi metallo-β-lactamase 1 (NDM-1) producing bacteria are resistant to most of the β-lactam antibiotics, and so far, no new compounds have been clinically tested against these bacteria. In this study, ethanol extracts from the leaves of 240 medicinal plant species were screened for antibacterial activity against an NDM-1 Escherichia coli strain. The extracts that showed antibacterial activity were then tested for minimum inhibitory concentrations (MICs) and zones of inhibition...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28877757/whole-genome-sequencing-of-esbl-producing-escherichia-coli-isolated-from-patients-farm-waste-and-canals-in-thailand
#3
Chakkaphan Runcharoen, Kathy E Raven, Sandra Reuter, Teemu Kallonen, Suporn Paksanont, Jeeranan Thammachote, Suthatip Anun, Beth Blane, Julian Parkhill, Sharon J Peacock, Narisara Chantratita
BACKGROUND: Tackling multidrug-resistant Escherichia coli requires evidence from One Health studies that capture numerous potential reservoirs in circumscribed geographic areas. METHODS: We conducted a survey of extended β-lactamase (ESBL)-producing E. coli isolated from patients, canals and livestock wastewater in eastern Thailand between 2014 and 2015, and analyzed isolates using whole genome sequencing. RESULTS: The bacterial collection of 149 isolates consisted of 84 isolates from a single hospital and 65 from the hospital sewer, canals and farm wastewater within a 20 km radius...
September 6, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28876169/ndm-1-hazard-in-the-balkan-states-evidence-of-the-first-outbreak-of-ndm-1-producing-klebsiella-pneumoniae-in-bulgaria
#4
Encho Savov, Lida Politi, Nicholas Spanakis, Angelina Trifonova, Elena Kioseva, Athanasios Tsakris
New Delhi MBL (NDM) carbapenemase-producing Klebsiella pneumoniae has become one of the most concerning multidrug-resistant pathogens. The Balkan counties are considered a reservoir for the spread of such strains based on several reports documenting NDM infections after hospitalization in this region. Nevertheless, NDM-producing K. pneumoniae have been only occasionally documented from Balkans. The current study documents the first polyclonal outbreak caused by NDM-1-producing K. pneumoniae in Bulgaria. From July 2015 to April 2016, all 25 single-patient carbapenem-nonsusceptible K...
September 6, 2017: Microbial Drug Resistance: MDR: Mechanisms, Epidemiology, and Disease
https://www.readbyqxmd.com/read/28876082/co-production-of-ndm-1-and-oxa-232-by-st16-klebsiella-pneumoniae-italy-2016
#5
Manuela Avolio, Carla Vignaroli, Massimo Crapis, Alessandro Camporese
Carbapenem-resistant Klebsiella pneumoniae strains, New Delhi metallo-β-lactamase-1 producers, are still rare in Italy, being endemic in Southeast Asiatic region. In October 2016, a multidrug-resistant K. pneumoniae was isolated from blood and urine of an Italian long-hospitalized patient with urosepsis without travel history abroad. To the best of our knowledge, this is the first report of bacteremia caused by an ST16 K. pneuomoniae New Delhi metallo-β-lactamase-1 and OXA-232 co-producing carbapenemase, in Italy...
September 6, 2017: Future Microbiology
https://www.readbyqxmd.com/read/28874377/high-level-resistance-to-colistin-mediated-by-various-mutations-in-the-crrb-gene-among-carbapenemase-producing-klebsiella-pneumoniae
#6
Aurélie Jayol, Patrice Nordmann, Adrian Brink, Maria-Virginia Villegas, Véronique Dubois, Laurent Poirel
Mutations in the crrAB genes encoding a two-component regulator involved in modifications of the lipopolysaccharide were searched for among a collection of colistin-resistant Klebsiella pneumoniae isolates. Four isolates respectively producing carbapenemases NDM-1, OXA-181, or KPC-2 showed mutated CrrB proteins compared to wild-type strains. Complementation assays with a wild-type CrrB protein restored the susceptibility to colistin in all cases, confirming the involvement of the identified substitutions in the resistance phenotype...
September 5, 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28859500/emergence-of-ndm-1-among-carbapenem-resistant-klebsiella-pneumoniae-in-iraqi-hospitals
#7
Nadheema Hammood Hussein
Carbapenems are the last drugs of choice apart from colistin against serious infections caused by Gram-negative bacteria. However, there are increasing number of reports indicating prevailing emergence of metallo-β-lactamase (MBL)-producing clinical isolates worldwide and among them New Delhi MBL (NDM) is the most prevalent one. This study reports NDM-1 for the first time among Klebsiella pneumoniae from hospitalized patients in Baghdad, Iraq. Fifty-five clinical isolates of K. pneumoniae resistant to carbapenem were investigated from burned wounds, sputum, and blood samples...
September 1, 2017: Acta Microbiologica et Immunologica Hungarica
https://www.readbyqxmd.com/read/28854628/genomic-epidemiology-of-ndm-1-encoding-plasmids-in-latin-american-clinical-isolates-reveals-insights-into-the-evolution-of-multidrug-resistance
#8
Ricaurte Alejandro Marquez-Ortiz, Leanne Haggerty, Narda Olarte, Carolina Duarte, Ulises Garza-Ramos, Jesus Silva-Sanchez, Betsy E Castro, Eby M Sim, Mauricio Beltran, María V Moncada, Alberto Valderrama, Jaime E Castellanos, Ian G Charles, Natasha Vanegas, Javier Escobar-Perez, Nicola K Petty
Bacteria that produce the broad-spectrum Carbapenem antibiotic New Delhi Metallo-β-lactamase (NDM) place a burden on health care systems worldwide, due to the limited treatment options for infections caused by them and the rapid global spread of this antibiotic resistance mechanism. Although it is believed that the associated resistance gene blaNDM-1 originated in Acinetobacter spp., the role of Enterobacteriaceae in its dissemination remains unclear. In this study, we used whole genome sequencing to investigate the dissemination dynamics of blaNDM-1-positive plasmids in a set of 21 clinical NDM-1-positive isolates from Colombia and Mexico (Providencia rettgeri, Klebsiella pneumoniae, and Acinetobacter baumannii) as well as six representative NDM-1-positive Escherichia coli transconjugants...
June 1, 2017: Genome Biology and Evolution
https://www.readbyqxmd.com/read/28839253/complete-sequences-of-two-novel-bla-ndm-1-harbouring-plasmids-from-two-acinetobacter-towneri-isolates-in-china-associated-with-the-acquisition-of-tn125
#9
Dayang Zou, Yong Huang, Wei Liu, Zhan Yang, Derong Dong, Simo Huang, Xiaoming He, Da Ao, Ningwei Liu, Shengshu Wang, Yong Wang, Yigang Tong, Jing Yuan, Liuyu Huang
Two novel New Delhi metallo-β-lactamase-1 (NDM-1)-positive plasmids containing a complete composite transposon, Tn125, from two respective Acinetobacter towneri isolates were characterized. Plasmid pNDM-GJ01 (30,293 bp) isolated from A. towneri G165 did not show homology to any known plasmid structure, except for the transposon Tn125 containing bla NDM-1. A novel repB gene and two XRE-type transcriptional regulators were found in pNDM-GJ01. Plasmid pNDM-GJ02 (62,011 bp) isolated from A. towneri G295 showed the highest homology to pBJAB0715 (41% coverage, 99% nucleotide identity)...
August 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28835636/potential-inhibitors-designed-against-ndm-1-type-metallo-%C3%AE-lactamases-an-attempt-to-enhance-efficacies-of-antibiotics-against-multi-drug-resistant-bacteria
#10
Asad U Khan, Abid Ali, Danishuddin, Gaurava Srivastava, Ashok Sharma
NDM-1 and its variants are the most prevalent types of metallo-β-lactamases, hydrolyze almost all antibiotics of β-lactam group leading to multiple-drug resistance in bacteria. No inhibitor has yet been obtained for NDM-1 or other class of metallo-β-lactamases. Therefore, strategies to identify novel anti-β-lactamase agents with specific mechanisms of action are the need of an hour. In this study, we have reported the discovery of novel non-β-lactam inhibitors against NDM-1 by multi-step virtual screening approach...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28830556/transmission-and-characterization-of-bla-ndm-1-in-enterobacter-cloacae-at-a-teaching-hospital-in-yunnan-china
#11
Na Du, Shumin Liu, Min Niu, Yong Duan, Shuangmeng Zhang, Jing Yao, Jian Mao, Ran Chen, Yan Du
BACKGROUND: In recent years, New Delhi metallo-beta-lactamases 1 (bla NDM-1) has been reported with increasing frequency and become prevalent. The present study was undertaken to investigate the epidemiological dissemination of the bla NDM-1 gene in Enterobacter cloacae isolates at a teaching hospital in Yunnan, China. METHODS: Antimicrobial susceptibility testing was performed using VITEK 2 system and E test gradient strips. The presence of integrons and insertion sequence common region 1 were examined by PCR and sequencing...
August 22, 2017: Annals of Clinical Microbiology and Antimicrobials
https://www.readbyqxmd.com/read/28820386/cost-of-nosocomial-outbreak-caused-by-ndm-1-containing-klebsiella-pneumoniae-in-the-netherlands-october-2015-january-2016
#12
Madelief Mollers, Suzanne P Lutgens, Annelot F Schoffelen, Peter M Schneeberger, Anita W M Suijkerbuijk
During October-December 2015, 29 patients in a hospital in the Netherlands acquired nosocomial infection with a multidrug-resistant, New Delhi-metallo-β-lactamase-positive Klebsiella pneumoniae strain. Extensive infection control measures were needed to stop this outbreak. The estimated economic impact of the outbreak was $804,263; highest costs were associated with hospital bed closures.
September 2017: Emerging Infectious Diseases
https://www.readbyqxmd.com/read/28809565/dipicolinic-acid-derivatives-as-inhibitors-of-new-delhi-metallo-%C3%AE-lactamase-1
#13
Allie Y Chen, Pei W Thomas, Alesha C Stewart, Alexander Bergstrom, Zishuo Cheng, Callie Miller, Christopher R Bethel, Steven H Marshall, Cy V Credille, Christopher L Riley, Richard C Page, Robert A Bonomo, Michael W Crowder, David L Tierney, Walter Fast, Seth M Cohen
The efficacy of β-lactam antibiotics is threatened by the emergence and global spread of metallo-β-lactamase (MBL) mediated resistance, specifically New Delhi metallo-β-lactamase-1 (NDM-1). By utilization of fragment-based drug discovery (FBDD), a new class of inhibitors for NDM-1 and two related β-lactamases, IMP-1 and VIM-2, was identified. On the basis of 2,6-dipicolinic acid (DPA), several libraries were synthesized for structure-activity relationship (SAR) analysis. Inhibitor 36 (IC50 = 80 nM) was identified to be highly selective for MBLs when compared to other Zn(II) metalloenzymes...
September 14, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28808891/nmr-backbone-resonance-assignment-of-new-delhi-metallo-beta-lactamase
#14
Chendie Yao, Qiong Wu, Guohua Xu, Conggang Li
The emerging of the New Delhi metallo-beta-lactamase (NDM-1) has become one of the greatest threats to the clinical treatment. Although the structure of NDM-1 has been determined by X-ray crystallography, the molecular mechanism and process of catalysis reaction remain elusive. NMR spectroscopy plays a unique role in the characterization of conformational dynamics. Here we report the backbone (1)H, (15)N and (13)C chemical shift assignments of NDM-1 by heteronuclear multidimensional NMR spectroscopy as well as its secondary structure in solution as predicted by TALOS+...
August 14, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28807096/a-five-year-surveillance-of-carbapenemase-producing-klebsiella-pneumoniae-in-a-pediatric-hospital-in-china-reveals-increased-predominance-of-ndm-1
#15
Fang Dong, Jie Lu, Yan Wang, Jin Shi, Jing Hui Zhen, Ping Chu, Yang Zhen, Shu Jing Han, Yong Li Guo, Wen Qi Song
OBJECTIVE: To characterize carbapenem (CPM)-non-susceptible Klebsiella pneumoniae (K. pneumoniae) and carbape-nemase produced by these strains isolated from Beijing Children's Hospital based on a five-year surveillance. METHODS: The Minimal Inhibition Concentration values for 15 antibiotics were assessed using the Phonix100 compact system. PCR amplification and DNA sequencing were used to detect genes encoding carbapenemases. WHONET 5.6 was finally used for resistance analysis...
August 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28789913/molecular-epidemiology-of-klebsiella-pneumoniae-invasive-infections-over-a-decade-at-kilifi-county-hospital-in-kenya
#16
Sonal P Henson, Christine J Boinett, Matthew J Ellington, Ngure Kagia, Salim Mwarumba, Sammy Nyongesa, Neema Mturi, Samuel Kariuki, J Anthony G Scott, Nicholas R Thomson, Susan C Morpeth
Multidrug resistant (MDR) Klebsiella pneumoniae is a common cause of nosocomial infections worldwide. Recent years have seen an explosion of resistance to extended-spectrum β-lactamases (ESBLs) and emergence of carbapenem resistance. Here, we examine 198 invasive K. pneumoniae isolates collected from over a decade in Kilifi County Hospital (KCH) in Kenya. We observe a significant increase in MDR K. pneumoniae isolates, particularly to third generation cephalosporins conferred by ESBLs. Using whole-genome sequences, we describe the population structure and the distribution of antimicrobial resistance genes within it...
July 22, 2017: International Journal of Medical Microbiology: IJMM
https://www.readbyqxmd.com/read/28776045/whole-genome-sequencing-of-human-clinical-klebsiella-pneumoniae-isolates-reveals-misidentification-and-misunderstandings-of-klebsiella-pneumoniae-klebsiella-variicola-and-klebsiella-quasipneumoniae
#17
S Wesley Long, Sarah E Linson, Matthew Ojeda Saavedra, Concepcion Cantu, James J Davis, Thomas Brettin, Randall J Olsen
Klebsiella pneumoniae is a major threat to public health, causing significant morbidity and mortality worldwide. The emergence of highly drug-resistant strains is particularly concerning. There has been a recognition and division of Klebsiella pneumoniae into three distinct phylogenetic groups: Klebsiella pneumoniae, Klebsiella variicola, and Klebsiella quasipneumoniae. K. variicola and K. quasipneumoniae have often been described as opportunistic pathogens that have less virulence in humans than K. pneumoniae does...
July 2017: MSphere
https://www.readbyqxmd.com/read/28717120/new-delhi-metallo-beta-lactamase-ndm-1-producing-klebsiella-pneumoniae-isolated-from-a-burned-patient
#18
Santiago Petersen-Morfin, Paola Bocanegra-Ibarias, Rayo Morfin-Otero, Elvira Garza-González, Hector Raul Perez-Gomez, Esteban González-Diaz, Sergio Esparza-Ahumada, Gerardo León-Garnica, Gabriel Amezcua-Salazar, Eduardo Rodriguez-Noriega
BACKGROUND Infections affecting burn patients are frequently caused by Staphylococcus aureus, Pseudomonas aeruginosa, and Enterobacteriaceae species. Infections with these pathogens have become increasingly difficult to treat due to evolving antibiotic resistance mechanisms, including the production of carbapenemases. CASE REPORT The present case report describes the evolution of a burn patient with polymicrobial healthcare-associated burn infections, including a bloodstream infection due to an emergent multidrug-resistant New Delhi metallo-beta-lactamase (NDM-1)-producing Klebsiella pneumoniae...
July 18, 2017: American Journal of Case Reports
https://www.readbyqxmd.com/read/28706386/alarming-emergence-molecular-characterization-and-outcome-of-blandm-1-in-patients-infected-with-multidrug-resistant-gram-negative-bacilli-in-a-tertiary-care-hospital
#19
Huma Naim, Meher Rizvi, Mohd Azam, Richa Gupta, Neelam Taneja, Indu Shukla, Haris M Khan
INTRODUCTION: This study was conducted to assess the prevalence of metallo-beta-lactamases (MBLs) in general and blaNDM-1 in particular. It also aimed at evaluating clinical characteristics and outcome in patients infected with MBLs. MATERIALS AND METHODS: A total of 116 carbapenem-resistant Gram-negative bacilli (CRGNB) were evaluated in the study. These CRGNB were tested for MBL production both phenotypically for MBLs and genotypically for blaNDM-1 gene by polymerase chain reaction (PCR)...
July 2017: Journal of Laboratory Physicians
https://www.readbyqxmd.com/read/28696242/pseudomonas-aeruginosa-clinical-isolates-in-nepal-coproducing-metallo-%C3%AE-lactamases-and-16s-rrna-methyltransferases
#20
Tatsuya Tada, Kayo Shimada, Kazuhito Satou, Takashi Hirano, Bharat M Pokhrel, Jeevan B Sherchand, Teruo Kirikae
A total of 11 multidrug-resistant Pseudomonas aeruginosa clinical isolates were obtained in Nepal. Four of these isolates harbored genes encoding one or more carbapenemases (DIM-1, NDM-1, and/or VIM-2), and five harbored genes encoding a 16S rRNA methyltransferase (RmtB4 or RmtF2). A novel RmtF variant, RmtF2, had a substitution (K65E) compared with the same gene in RmtF. To our knowledge, this is the first report describing carbapenemase- and 16S rRNA methyltransferase-coproducing P. aeruginosa clinical isolates in Nepal...
September 2017: Antimicrobial Agents and Chemotherapy
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