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Antimicrobial Agents and Chemotherapy, March 1999, p. 573-581, Vol. 43, No. 3
Service de Bactériologie-Virologie,
Received 19 May 1998/Returned for modification 21 October
1998/Accepted 13 December 1998
A clinical isolate, Escherichia coli MG-1, isolated
from a 4-month-old Vietnamese orphan child, produced a
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Molecular and Biochemical Characterization of
VEB-1, a Novel Class A Extended-Spectrum
-Lactamase Encoded by
an Escherichia coli Integron Gene
-lactamase
conferring resistance to extended-spectrum cephalosporins and
aztreonam. In a disk diffusion test, a typical synergistic effect
between ceftazidime or aztreonam and clavulanic acid was observed along with an unusual synergy between cefoxitin and cefuroxime. The gene for
VEB-1 (Vietnamese extended-spectrum
-lactamase) was cloned and
expressed in E. coli JM109. The recombinant plasmid pRLT1
produced a
-lactamase with a pI of 5.35 and conferred
high-level resistance to extended-spectrum (or oxyimino) cephalosporins
and to aztreonam. Vmax values for
extended-spectrum cephalosporins were uncommonly high, while the
affinity of the enzyme for ceftazidime and aztreonam was relatively
low. blaVEB-1 showed significant homology at
the DNA level with only blaPER-1 and
blaPER-2. Analysis of the deduced protein
sequence showed that VEB-1 is a class A penicillinase having very low
levels of homology with any other known
-lactamases. The
highest percentage of amino acid identity was 38% with PER-1 or PER-2,
two uncommon class A extended-spectrum enzymes. Exploration of the
genetic environment of blaVEB-1 revealed the
presence of gene cassette features, i.e., (i) a 59-base element associated with blaVEB-1; (ii) a second 59-base
element just upstream of blaVEB-1, likely
belonging to the aacA1-orfG gene cassette; (iii) two core
sites (GTTRRRY) on both sides of blaVEB-1; and (iv) a second antibiotic resistance gene 3' of
blaVEB-1, aadB. blaVEB-1 may therefore be the first class A
extended-spectrum
-lactamase that is part of a gene
cassette, which itself is likely to be located on a class 1 integron,
as sulfamide resistance may indicate. Furthermore,
blaVEB-1 is encoded on a large (>100-kb) transferable plasmid found in a Klebsiella pneumoniae MG-2
isolated at the same time from the same patient, indicating a
horizontal gene transfer.
*
Corresponding author. Mailing address: Service de
Bactériologie-Virologie, Hôpital de Bicêtre, 78 rue
du Général Leclerc, 94275 Le Kremlin-Bicêtre, France.
Phone: 33-1-45-21-36-32. Fax: 33-1-45-21-63-40. E-mail:
nordmann.patrice{at}bct.ap-hop-paris.fr.
Antimicrobial Agents and Chemotherapy, March 1999, p. 573-581, Vol. 43, No. 3
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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