Presence of New Delhi metallo-β-lactamase gene (NDM-1) in a clinical isolate of Acinetobacter junii in Argentina.
Ontology highlight
ABSTRACT:
SUBMITTER: Montana S
PROVIDER: S-EPMC4877398 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
Publications
Presence of New Delhi metallo-β-lactamase gene (NDM-1) in a clinical isolate of Acinetobacter junii in Argentina.
Montaña S S Cittadini R R Del Castillo M M Uong S S Lazzaro T T Almuzara M M Barberis C C Vay C C Ramírez M S MS
New microbes and new infections 20160223
Similar Datasets
Project description:A 4-year surveillance of carbapenem-resistant Acinetobacter spp. isolates in Argentina identified 40 strains carrying blaNDM-1 Genome sequencing revealed that most were Acinetobacter baumannii, whereas seven represented other Acinetobacter spp. The A. baumannii genomes were closely related, suggesting recent spread. blaNDM-1 was located in the chromosome of A. baumannii strains and on a plasmid in non-A. baumannii strains. A resistance gene island carrying blaPER-7 and other resistance determinants was found on a plasmid in some A. baumannii strains.
| S-EPMC7179578 | biostudies-literature
Project description:Antibiotic resistance in bacterial pathogens poses a serious threat to human health and the metallo-β-lactamase (MBL) enzymes are responsible for much of this resistance. The recently identified New Delhi MBL 1 (NDM-1) is a novel member of this family that is capable of hydrolysing a wide variety of clinically important antibiotics. Here, the crystal structure of NDM-1 from Klebsiella pneumoniae is reported and its structure and active site are discussed in the context of other recently deposited coordinates of NDM-1.
| S-EPMC3212353 | biostudies-literature
Project description:The objective of this study was the phenotypic and genotypic characterization of a carbapenem resistant Acinetobacter baumannii (CRAB) isolate. The isolate, recovered in Northern Spain in 2019, was identified by MALDI-TOF to the species level. Antimicrobial susceptibility testing was performed using the Phoenix BD NMIC-502 Panel, E-test, and broth microdilution methods. The presence of a metallo-β-lactamase (MBL) was verified by PCR and immunochromatographic assays. The genetic location of the MBL was confirmed using S1-pulsed-field gel electrophoresis (S1-PFGE) followed by Southern blot hybridization. Whole genome sequencing (WGS) was completed using the Miseq and MinION platforms, followed by core-genome MLST (cgMLST) and seven-locus MLST analysis. The CRAB was assigned ST85 (Pasteur scheme) and ST957 (Oxford scheme) representing international clone (IC) 9 and harbored the intrinsic β-lactamase OXA-94 with ISAba1 upstream of it, and the MBL bla NDM-6. Hybridization experiments revealed that the bla NDM-6 was encoded on the chromosome. Using WGS the bla NDM-6 environment could be identified arranged in the following order: ISAba14, aphA6, ISAba125, bla NDM-6, ble MBL, trpF, dsbC, cutA, and ISAba14. Downstream, a 10,462 bp duplication was identified, including a second copy of bla NDM-6 in the following genetic composition: ISAba125, bla NDM-6, ble MBL, trpF, dsbC, cutA, and ISAba14. To our knowledge, this is the first description of bla NDM-6 in A. baumannii. The MBL was present in two copies in the chromosome in a new genetic environment associated with IS elements highlighting the contribution of mobile genetic elements in the dissemination of this gene.
| S-EPMC7683408 | biostudies-literature
Project description:'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. coli BL21 (DE3)/pET30a-NDM-1 and a clinical isolate of P. aeruginosa with blaNDM-1. Flexible docking and partial charge study suggested the interaction between oligopeptide and NDM-1. Three types of action effects, hydrogen bond, electrostatic effect and π-π interaction, contributed to the inhibitory activities.
| S-EPMC5441612 | biostudies-literature
Project description:A novel New Delhi metallo-β-lactamase variant, NDM-12, was identified in a carbapenem-resistant Escherichia coli clinical isolate obtained from a urine sample from a patient in Nepal. NDM-12 differed from NDM-1 by two amino acid substitutions (M154L and G222D). The enzymatic activities of NDM-12 against β-lactams were similar to those of NDM-1, although NDM-12 showed lower kcat/Km ratios for all β-lactams tested except doripenem. The blaNDM-12 gene was located in a plasmid of 160 kb.
| S-EPMC4187903 | biostudies-literature
Project description:UnlabelledBACKGOUND & OBJECTIVES: Resistance to carbapenems in Gram-negative bacteria conferred by NDM-1 is a global health problem. We investigated the occurrence of NDM-1 in clinical isolates of Gram-negative bacilli in a tertiary care hospital in Kashmir valley, India.MethodsGram-negative bacilli from different clinical isolates were included in the study. Antimicrobial susceptibility was performed by Kirby Bauer disk diffusion method and interpreted using Clinical Laboratory Standards Institute (CLSI) guidelines. Isolates resistant to carbapenems were subjected to different phenotypic test such as modified Hodge test (MHT), boronic acid and oxacillin based MHT ( BA-MHT and OXA-MHT), combined disk test and minimum inhibitory concentration (MIC) with imipenem and imipenem -EDTA for determination of class B metallo enzymes. Presence of blaNDM-1 gene was established by PCR and confirmed by sequencing.ResultsOf the total 1625 Gram-negative isolates received, 100 were resistant to imipenem. Of the 100 isolates, 55 (55%) were positive by modified Hodge test indicating carbapenemase production. Of the 100 isolates tested by MHT, BA-MHT and OXA-MHT, 29 (29%) isolates belonged to Class A and 15 (15%) to Class B, while 56 (56%) isolates were negative. Of the 15 class B metallo beta lactamase producers, nine carried the bla(NDM-1) gene. NDM-1 was found among Escherichia coli (2 isolates), Klebsiella pneumoniae (2 isolates), Citrobacter freundii (3 isolates), Acinetobacter spp (1 isolate), and one isolate of Pseudomonas aeruginosa. Isolates were resistant to all antibiotic tested except polymyxin B and tigecycline.Interpretation & conclusionsOur study showed the presence of clinical isolates expressing NDM-1 in Srinagar, Jammu & Kashmir, India. These isolates harbour plasmid mediated multiple drug resistant determinants and can disseminate easily across several unrelated genera. To halt their spread, early identification of these isolates is mandatory.
| S-EPMC4311323 | biostudies-literature
Project description:New Delhi Metallo-β-lactamase-1 (NDM-1) is the most prevalent type of metallo-β-lactamase, able to hydrolyze almost all antibiotics of the β-lactam group, leading to multidrug-resistant bacteria. To date, there are no clinically relevant inhibitors to fight NDM-1. The use of dromedary polyclonal antibody inhibitors against NDM-1 represents a promising new class of molecules with inhibitory activity. In the current study, immunoreactivities of dromedary Immunoglobulin G (IgG) isotypes containing heavy-chain and conventional antibodies were tested after successful immunization of dromedary using increasing amounts of the recombinant NDM-1 enzyme. Inhibition kinetic assays, performed using a spectrophotometric method with nitrocefin as a reporter substrate, demonstrated that IgG1, IgG2, and IgG3 were able to inhibit not only the hydrolytic activity of NDM-1 but also Verona integron-encoded metallo-β-lactamase (VIM-1) (subclass B1) and L1 metallo-β-lactamase (L1) (subclass B3) with inhibitory concentration (IC50) values ranging from 100 to 0.04 μM. Investigations on the ability of IgG subclasses to reduce the growth of recombinant Escherichia coli BL21(DE3)/codon plus cells containing the recombinant plasmid expressing NDM-1, L1, or VIM-1 showed that the addition of IgGs (4 and 8 mg/L) to the cell culture was unable to restore the susceptibility of carbapenems. Interestingly, IgGs were able to interact with NDM-1, L1, and VIM-1 when tested on the periplasm extract of each cultured strain. The inhibitory concentration was in the micromolar range for all β-lactams tested. A visualization of the 3D structural basis using the three enzyme Protein Data Bank (PDB) files supports preliminarily the recorded inhibition of the three MBLs.
| S-EPMC7584030 | biostudies-literature
Project description:The effectiveness of all antibiotics in the β-lactam group to cure bacterial infections has been impaired by the introduction of the New Delhi Metallo-β-lactamase (NDM-1) enzyme. Attempts have been made to discover a potent chemical as an inhibitor to this enzyme in order to restore the efficacy of antibiotics. However, it has been a challenging task to develop broad-spectrum inhibitors of metallo-β-lactamases. Lack of sequence homology across metallo-β-lactamases (MBLs), the rapidly evolving active site of the enzyme, and structural similarities between human enzymes and metallo-β-lactamases, are the primary causes for the difficulty in the development of these inhibitors. Therefore, it is imperative to concentrate on the discovery of an effective NDM-1 inhibitor. This study used various in silico approaches, including molecular docking and molecular dynamics simulations, to investigate the potential of phytochemicals to inhibit the NDM-1 enzyme. For this purpose, a library of about 59,000 phytochemicals was created from the literature and other databases, including FoodB, IMPPAT, and Phenol-Explorer. A physiochemical and pharmacokinetics analysis was performed to determine possible toxicity and mutagenicity of the ligands. Following the virtual screening, phytochemicals were assessed for their binding with NDM-1using docking scores, RMSD values, and other critical parameters. The docking score was determined by selecting the best conformation of the protein-ligand complex. Three phytochemicals, i.e., butein (polyphenol), monodemethylcurcumin (polyphenol), and rosmarinic acid (polyphenol) were identified as result of pharmacokinetics and molecular docking studies. Furthermore, molecular dynamics simulations were performed to determine structural stabilities of the protein-ligand complexes. Monodemethylcurcumin, butein, and rosmarinic acid were identified as potential inhibitors of NDM-1 based on their low RMSD, RMSF, hydrogen bond count, average Coulomb-Schrödinger interaction energy, and Lennard-Jones-Schrödinger interaction energy. The present investigation suggested that these phytochemicals might be promising candidates for future NDM-1 medication development to respond to antibiotic resistance.
| S-EPMC10610165 | biostudies-literature
Project description:Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly spreading and taking a staggering toll on all health care systems, largely due to the dissemination of genes coding for potent carbapenemases. An important family of carbapenemases are the Zn(II)-dependent β-lactamases, known as metallo-β-lactamases (MBLs). Among them, the New Delhi metallo-β-lactamase (NDM) has experienced the fastest and widest geographical spread. While other clinically important MBLs are soluble periplasmic enzymes, NDMs are lipoproteins anchored to the outer membrane in Gram-negative bacteria. This unique cellular localization endows NDMs with enhanced stability upon the Zn(II) starvation elicited by the immune system response at the sites of infection. Since the first report of NDM-1, new allelic variants (16 in total) have been identified in clinical isolates differing by a limited number of substitutions. Here, we show that these variants have evolved by accumulating mutations that enhance their stability or the Zn(II) binding affinity in vivo, overriding the most common evolutionary pressure acting on catalytic efficiency. We identified the ubiquitous substitution M154L as responsible for improving the Zn(II) binding capabilities of the NDM variants. These results also reveal that Zn(II) deprivation imposes a strict constraint on the evolution of this MBL, overriding the most common pressures acting on catalytic performance, and shed light on possible inhibitory strategies.
| S-EPMC5740384 | biostudies-literature
Project description: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. The isolate that was assigned to ST1114, exhibited high level resistance to all β-lactams tested, including aztreonam and carbapenems. The gene of blaNDM-20 was located on an IncX3-type plasmid, surrounded by multiple insertion sequences. Sequencing analysis demonstrated that blaNDM-20 contained three point mutations at positions 262 (G→T), 460 (A→C), and 809 (G→A), compared with blaNDM-1, and just one point mutation at position 809 (G→A), relative to blaNDM-5. Functional analysis revealed that the blaNDM-20 transformant, DH5α+pHSG398/NDM-20, exhibited a higher resistance to ertapenem than that of blaNDM-1 transformant DH5α+pHSG398/NDM-1. Kinetic parameter analysis showed that NDM-20 had increased enzymatic activity against some penicillins and cephalosporins but decreased carbapenemase activity relative to NDM-5. The identification of NDM-20 further confirms the evolution and prevalence of NDM variants in bacteria of food-animal origin.
| S-EPMC5826333 | biostudies-literature