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Shui Liu, Yonglin Zhou, Xiaodi Niu, Tingting Wang, Jiyun Li, Zhongjie Liu, Jianfeng Wang, Shusheng Tang, Yang Wang, Xuming Deng
The emergence of plasmid-mediated New Delhi metallo-β-lactamase-1 (NDM-1) in carbapenem-resistant Gram-negative pathogens is an increasing clinical threat. Here we report the discovery of an NDM-1 inhibitor, magnolol, through enzyme inhibition screening. We showed that magnolol significantly inhibited NDM enzyme activity (IC50  = 6.47 µg/mL), and it restored the activity of meropenem against Escherichia coli ZC-YN3, an NDM-1-producing E. coli isolate, in in vitro antibacterial activity assays. Magnolol lacked direct antibacterial activity, but compared with meropenem alone, it reduced the MICs of meropenem against E...
December 2018: Cell Death Discovery
Martin Everett, Nicolas Sprynski, Alicia Coelho, Jérôme Castandet, Maëlle Bayet, Juliette Bougnon, Clarisse Lozano, David T Davies, Simon Leiris, Magdalena Zalacain, Ian Morrissey, Sophie Magnet, Kirsty Holden, Peter Warn, Filomena De Luca, Jean-Denis Docquier, Marc Lemonnier
Infections caused by carbapenem-resistant Enterobacteriaceae (CRE) are increasingly prevalent and have become a major worldwide threat to human health. Carbapenem resistance is driven primarily by the acquisition of β-lactamase enzymes which are able to degrade carbapenem antibiotics (hence termed carbapenemases) and can result in high levels of resistance and treatment failure. Clinically relevant carbapenemases include both serine-β-lactamases (SBLs, e.g. KPC-2 and OXA-48) and metallo-β-lactamases (MBLs), such as NDM-1...
March 12, 2018: Antimicrobial Agents and Chemotherapy
Carole Ayoub Moubareck, Shaimaa F Mouftah, Tibor Pál, Akela Ghazawi, Dalal H Halat, Anju Nabi, Mouza A AlSharhan, Zulfa O AlDeesi, Christabel C Peters, Handan Celiloglu, Manjunath Sannegowda, Dolla K Sarkis, Ágnes Sonnevend
Few studies have addressed the molecular epidemiology of carbapenem resistant Enterobacteriaceae (CRE) isolates in the Arabian Peninsula, and such investigations have been missing from Dubai, a major economical, tourism and medical centre of the region. The antibiotic susceptibility, the carbapenemase type produced, and the clonality of 89 CRE strains isolated in five major Dubai hospitals in June 2015 - June 2016 were determined. Thirty three percent of the collection of 70 K. pneumoniae, 13 E. coli and 6 other Enterobacteriaceae were extremely drug resistant, 27% were resistant to colistin, and 4...
March 9, 2018: International Journal of Antimicrobial Agents
Barbara Piccini, Caterina Coviello, Livia Drovandi, Artuso Rosangela, Francesca Monzali, Emilio Casalini, Sabrina Giglio, Sonia Toni, Carlo Dani
Neonatal diabetes mellitus (NDM) is a monogenic form of diabetes occurring within 6 months from birth. NDM can be permanent or transient (TNDM). We report the case of a preterm infant with TNDM due to an ABCC8 mutation identified by next-generation sequencing. The pancreatic adenosine triphosphate (ATP)-sensitive K+ (K-ATP) channel is a key regulator of insulin secretion. Gain-of-function mutations in the genes encoding the Kir6.2 (KCNJ11) and SUR1 (ABCC8) subunits of the channel cause neonatal diabetes. The patient was successfully managed with insulin lispro at a 1:100 dilution, drawn up in an insulin pen injector with a 4-mm needle...
January 2018: American Journal of Perinatology Reports
Inés Bado, Romina Papa Ezdra, Nicolás Cordeiro, Matilde Outeda, Leticia Caiata, Virginia García-Fulgueiras, Verónica Seija, Rafael Vignoli
OBJECTIVES: The objective of the present study was to characterise the mechanisms underlying quinolone and oxyimino-cephalosporin resistance in a Citrobacter freundii clinical isolate obtained from the ICU in Uruguay's University Hospital. METHODS: Citrobacter freundii strain CF638 was isolated from a urine culture. Identification and susceptibility testing were performed using the VITEK® 2 system, and MIC determination and disc diffusion assay, respectively. Resistance genes and mobile genetic elements were identified, by PCR and sequencing...
March 8, 2018: Journal of Global Antimicrobial Resistance
Hamid Solgi, Farzad Badmasti, Christian G Giske, Shadi Aghamohammad, Fereshteh Shahcheraghi
Objectives: Despite the fact that the blaOXA-48 and blaNDM-1 genes have successfully disseminated among Klebsiella pneumoniae isolates worldwide, outbreaks remain unidentified in Iran. Here we examined the molecular epidemiology of 96 carbapenem-resistant K. pneumoniae recovered from an Iranian hospital. Methods: A total of 96 non-replicate carbapenem-resistant K. pneumoniae were recovered from clinical specimens in a university hospital. Detection of ESBLs and carbapenemases produced by studied strains was performed using PCR and DNA sequencing...
March 6, 2018: Journal of Antimicrobial Chemotherapy
Zhihai Liu, Jiyun Li, Xiaoming Wang, Dejun Liu, Yuebin Ke, Yang Wang, Jianzhong Shen
The spread of carbapenem-resistant Enterobacteriaceae (CRE) mediated by New Delhi metallo-β-lactamase (NDM) poses a serious challenge to clinicians and has become a major public health concern. NDM has been evolving into variants that possess different hydrolysis activity toward antibiotics, so as to affect treatment strategy. In addition, very few studies on NDM variants have focused on animal-derived bacterial isolates. Our study reports a novel NDM variant, NDM-20, in an isolate of Escherichia coli CCD1 recovered from the food animal swine in China...
2018: Frontiers in Microbiology
Michael A Pfaller, Michael D Huband, Rodrigo E Mendes, Robert K Flamm, Mariana Castanheira
We evaluated meropenem-vaborbactam activity against 11,559 Enterobacteriaceae isolates, including 330 carbapenem-resistant phenotypes (CRE) and carbapenemase genotypes collected worldwide during 2015. Meropenem-vaborbactam (inhibitor at 8 mg/L) and comparators were susceptibility tested using reference broth microdilution methods. CRE isolates were screened for the presence of genes encoding carbapenemases and 292 (88.5%) of the CRE isolates carried these resistance genes. A total of 209 (63.3% of the CRE; 1...
March 3, 2018: International Journal of Antimicrobial Agents
Qiu E Yang, Siham Rajab Agouri, Jonathan Mark Tyrrell, Timothy Rutland Walsh
The occurrence of heavy metal resistance genes in multi-resistant Enterobacteriaceae possessing bla NDM-1 or bla CTX-M-15 genes were examined by PCR and S1-PFGE. When compared with clinical susceptible isolates (10.0-30.0%), the pcoA, merA, silC and arsA genes occurred with higher frequencies in bla NDM-1 (48.8-71.8%) and bla CTX-M-15 (19.4-52.8%) positive isolates, and they are mostly located on plasmids. Given the high association of metal resistance genes with multidrug resistant Enterobacteriaceae, the use of heavy metals in hospitals and the environment needs increased vigilance...
March 5, 2018: Antimicrobial Agents and Chemotherapy
Torunn Pedersen, John Osei Sekyere, Usha Govinden, Krishnee Moodley, Audun Sivertsen, Ørjan Samuelsen, Sabiha Yusuf Essack, Arnfinn Sundsfjord
Whole-genome sequence analyses revealed the presence of bla NDM-1 ( n =31), bla GES-5 ( n =8), bla OXA-232 ( n =1), or bla NDM-5 ( n =1) in extensively drug-resistant and pandrug-resistant Enterobacteriaceae isolated from in-patients in 10 private hospitals (2012-2013) in Durban, South Africa. Two novel NDM-1 encoding plasmids from Klebsiella pneumoniae were closed by PacBio sequencing. In p19-10_01 (IncFIB(K), 223.434 bp) bla NDM-1 was part of a Tn 1548 -like structure (16.276 bp) delineated by IS 26 The multireplicon plasmid p18-43_01 (IncR_1/IncFIB(pB171)/IncFII(Yp); 212...
March 5, 2018: Antimicrobial Agents and Chemotherapy
Qian Wang, Yuan He, Rui Lu, Wen-Ming Wang, Ke-Wu Yang, Hai Ming Fan, Yi Jin, G Michael Blackburn
The New Delhi metallo-β-lactamase (NDM-1) is an important clinical target for antimicrobial research, but there are insufficient clinically useful inhibitors and the details of NDM-1 enzyme catalysis remain unclear. The aim of this work is to provide a thermodynamic profile of NDM-1 catalysed hydrolysis of β-lactams using an isothermal titration calorimetry (ITC) approach and to apply this new method to the identification of new low-molecular-weight dicarboxylic acid inhibitors. The results reveal that hydrolysis of penicillin G and imipenem by NDM-1 share the same thermodynamic features with a significant intrinsic enthalpy change and the release of one proton into solution, while NDM-1 hydrolysis of cefazolin exhibits a different mechanism with a smaller enthalpy change and the release of two protons...
March 5, 2018: Bioscience Reports
Maria Giufrè, Giulia Errico, Marisa Accogli, Monica Monaco, Laura Villa, Maria Antonietta Distasi, Tito Del Gaudio, Annalisa Pantosti, Alessandra Carattoli, Marina Cerquetti
The emergence of carbapenemase-producing Enterobacteriaceae (CPE) is a critical concern worldwide. In Italy, CPE isolates are very frequent with the KPC types strongly predominant whereas the New Delhi metallo-β-lactamase (NDM) enzymes are extremely rare. In this study, we report the first detection of NDM-5-producing Escherichia coli sequence type (ST) 167 isolates from two patients with urinary tract infection (Ec001and Ec002 from urines) including one with colonization (Ec003 from faeces) admitted to the same hospital in 2017 two months apart...
February 28, 2018: International Journal of Antimicrobial Agents
Hanna E Sidjabat, Jolene Gien, David Kvaskoff, Keith Ashman, Kanchan Vaswani, Sarah Reed, Ross P McGeary, David L Paterson, Amanda Bordin, Gerhard Schenk
Antibiotic resistance associated with the clinically significant carbapenemases KPC, NDM and OXA-48 in Enterobacteriaceae is emerging as worldwide. In Australia, IMP-producing Enterobacteriaceae are the most prevalent carbapenemase-producing Enterobacteriaceae (CPE). Genomic characteristics of such CPE are well described, but the corresponding proteome is poorly characterised. We have thus developed a method to analyse dynamic changes in the proteome of CPE under antibiotic pressure. Specifically, we have investigated the effect of meropenem at sub-lethal concentrations to develop a better understanding of how antibiotic pressure leads to resistance...
March 1, 2018: Scientific Reports
Yang Li, Jing Chen, Liyun Jiang, Gexia Qiao
Patterns of biodiversity and endemism are important and form the foundation for biogeography and conservation studies. Hormaphidinae is an aphid group mainly distributed in the Sino-Japanese, Oriental, and Nearctic zoogeographic realms. To infer the areas of endemism of Hormaphidinae aphids in the Sino-Japanese and Oriental realms, we employed a geographical distribution dataset covering all 225 species in subfamily Hormaphidinae. In total, 1,245 distribution occurrence records for all species were analyzed in addition to the number of species in a certain grid cell to calculate species richness...
December 2017: Current Zoology
Philip Hinchliffe, Carol A Tanner, Anthony P Krismanich, Geneviève Labbé, Valerie J Goodfellow, Laura Marrone, Ahmed Desoky, Karina Calvopiña, Emily E Whittle, Fanxing Zeng, Matthew Avison, Niels C Bols, Stefan Siemann, James Spencer, Gary Igor Dmitrienko
There are currently no clinically available inhibitors of metallo-β-lactamases (MBLs), enzymes which hydrolyze β-lactam antibiotics and confer resistance on Gram-negative bacteria. Here we present 6-phosphonomethylpyridine-2-carboxylates (PMPCs) as potent inhibitors of subclass B1 (IMP-1, VIM-2, NDM-1) and B3 (L1) MBLs. Inhibition followed a competitive, slow-binding model without an isomerization step (IC50 values 0.3 - 7.2 µM; Ki 0.03 - 1.5 µM). Minimum inhibitory concentration assays demonstrated potentiation of β-lactam (meropenem) activity against MBL-producing bacteria, including clinical isolates, at concentrations where eukaryotic cells remain viable...
February 27, 2018: Biochemistry
Jade E McLellan, Joshua I Pitcher, Susan A Ballard, Elizabeth A Grabsch, Jan M Bell, Mary Barton, M Lindsay Grayson
Background: Antibiotic misuse in food-producing animals is potentially associated with human acquisition of multidrug-resistant (MDR; resistance to ≥ 3 drug classes) bacteria via the food chain. We aimed to determine if MDR Gram-negative (GNB) organisms are present in fresh Australian chicken and pork products. Methods: We sampled raw, chicken drumsticks (CD) and pork ribs (PR) from 30 local supermarkets/butchers across Melbourne on two occasions. Specimens were sub-cultured onto selective media for third-generation cephalosporin-resistant (3GCR) GNBs, with species identification and antibiotic susceptibility determined for all unique colonies...
2018: Antimicrobial Resistance and Infection Control
Ryota Gomi, Tomonari Matsuda, Masaki Yamamoto, Pei-Hsin Chou, Michio Tanaka, Satoshi Ichiyama, Minoru Yoneda, Yasufumi Matsumura
Wastewater is considered a major source of antibiotic-resistant bacteria released into the environment. Here, we characterized carbapenemase-producing Enterobacteriaceae (CPE) in wastewater by whole-genome analysis. Wastewater samples (n = 40) were collected from municipal wastewater treatment plants and hospital wastewater in Japan and Taiwan. Samples were screened for CPE using selective media, and the obtained isolates were sequenced using an Illumina MiSeq. The isolates (n = 45) included the following microorganisms: Klebsiella quasipneumoniae (n = 12), Escherichia coli (n = 10), Enterobacter cloacae complex (n = 10), Klebsiella pneumoniae (n = 8), Klebsiella variicola (n = 2), Raoultella ornithinolytica (n = 1), Citrobacter freundii (n = 1), and Citrobacter amalonaticus (n = 1)...
February 26, 2018: Antimicrobial Agents and Chemotherapy
Eun-Jeong Yoon, Ji Woo Yang, Jung Ok Kim, Hyukmin Lee, Kwang Jun Lee, Seok Hoon Jeong
AIM: To assess the epidemiology of carbapenemase-producing Enterobacteriaceae (CPE) in South Korea. MATERIALS & METHODS: From 2011 to 2015, 2487 carbapenem-nonsusceptible Enterobacteriaceae were collected through the Korean National Laboratory Surveillance System. Disk-diffusion for antimicrobial susceptibility, PCR/sequencing to detect carbapenemase genes and multilocus sequence typing for molecular epidemiology were carried out. RESULTS: The number of carbapenem-nonsusceptible Enterobacteriaceae was increasing approximately 1...
February 26, 2018: Future Microbiology
Zhu-Jun Yu, Sha Liu, Shu Zhou, Hui Li, Fan Yang, Ling-Ling Yang, Yong Wu, Li Guo, Guo-Bo Li
Rosmarinic acid (RA), a polyphenolic phytochemical, has broad-spectrum biological and pharmacological activity. A virtual target screening method termed IFPTarget combined with enzyme inhibition assays led to the identification of the clinically relevant metallo-β-lactamase (MBL) VIM-2 as one of unexploited targets of RA. The enzyme kinetic studies indicated that RA is a fully reversible, substrate-competitive VIM-2 inhibitor. The isothermal titration calorimetry (ITC) analyses revealed that the initial binding of RA to VIM-2 is mainly due to enthalpy contribution...
February 14, 2018: Bioorganic & Medicinal Chemistry Letters
Amna E Al-Baloushi, Tibor Pál, Akela Ghazawi, Agnes Sonnevend
Enterobacteriaceae co-producing NDM- and OXA-48-type carbapenemases were encountered in higher frequency in the United Arab Emirates (UAE) than in the neighboring countries in our earlier study. The aim of this investigation was to characterize the seven double carbapenemase producer Klebsiella pneumoniae found in the region to assess factors contributing to their emergence. Three K. pneumoniae ST14 isolated in the UAE harboring blaNDM-1 on IncHI1b and blaOXA-232 on IncColE plasmids were clonally related. Furthermore, two K...
February 23, 2018: Acta Microbiologica et Immunologica Hungarica
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