Periods and by way of the action of a multimodal antiangiogenic therapeutic.NIHPA Author Manuscript NIHPA Author Manuscript NIHPA Author ManuscriptAcknowledgmentsThe authors thank the Edward N. Della L. Thome Memorial Foundation (Bank of America, Trustee) Awards Program in AMD Research, the NIH (1R21EY02298601 and R01EY012609), plus the Wallace H. Coulter Foundation for assistance of this perform.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 1999, p. 57381 00664804/99/ 04.00 0 Copyright 1999, American Society for Microbiology. All Rights Reserved.Vol. 43, No.Molecular and Biochemical Characterization of VEB1, a Novel Class A ExtendedSpectrum Lactamase Encoded by an Escherichia coli Integron GeneLAURENT POIREL,1 THIERRY NAAS,2 MICHELE GUIBERT,two EL BACHIR CHAIBI,3 ROGER LABIA,three AND PATRICE NORDMANN1 Service de BacteriologieVirologie, Hopital de Bicetre, Faculte de Medecine ParisSud, 94275 Le KremlinBicetre,1 ^ ^ ^ Service de BacteriologieVirologie, Hopital Antoine Beclere, Faculte de Medecine ParisSud 92141 ^ ` Clamart Cedex,2 and Chimie et Biologie des Substances Actives, UMR 175 CNRSMNHN, 29000 Quimper,three FranceReceived 19 May 1998/Returned for modification 21 October 1998/Accepted 13 DecemberA clinical isolate, Escherichia coli MG1, isolated from a 4monthold Vietnamese orphan kid, made a lactamase conferring resistance to extendedspectrum cephalosporins and aztreonam. Inside a disk diffusion test, a typical synergistic impact among ceftazidime or aztreonam and clavulanic acid was observed in conjunction with an unusual synergy between cefoxitin and cefuroxime. The gene for VEB1 (Vietnamese extendedspectrum lactamase) was cloned and expressed in E. coli JM109. The recombinant plasmid pRLT1 produced a lactamase with a pI of five.35 and conferred highlevel resistance to extendedspectrum (or oxyimino) cephalosporins and to aztreonam. Vmax values for extendedspectrum cephalosporins have been uncommonly high, though the affinity on the enzyme for ceftazidime and aztreonam was reasonably low. blaVEB1 showed significant homology at the DNA level with only blaPER1 and blaPER2. Analysis of the deduced protein sequence showed that VEB1 is often a class A penicillinase obtaining pretty low levels of homology with any other recognized lactamases. The highest percentage of amino acid identity was 38 with PER1 or PER2, two uncommon class A extendedspectrum enzymes.1,2-Benzisoxazol-6-amine uses Exploration with the genetic environment of blaVEB1 revealed the presence of gene cassette features, i.156496-89-8 Chemical name e.PMID:23075432 , (i) a 59base element connected with blaVEB1; (ii) a second 59base element just upstream of blaVEB1, probably belonging towards the aacA1orfG gene cassette; (iii) two core web sites (GTTRRRY) on each sides of blaVEB1; and (iv) a second antibiotic resistance gene three of blaVEB1, aadB. blaVEB1 may well hence be the first class A extendedspectrum lactamase that is component of a gene cassette, which itself is probably to be located on a class 1 integron, as sulfamide resistance could indicate. Furthermore, blaVEB1 is encoded on a big (100kb) transferable plasmid located inside a Klebsiella pneumoniae MG2 isolated at the same time from the similar patient, indicating a horizontal gene transfer. While naturally susceptible to extendedspectrum cephalosporins, Escherichia coli strains may develop into resistant to these lactams by many mechanisms, mostly alterations in outer membrane proteins, overproduction of cephalosporinase (chromosomal or plasmid mediated), or production of an extendedspectrum lactamase (ESBL). ESBLs are enzymes capable of hydrolyzing oxy.
