Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, August 2001, p. 2269-2275, Vol. 45, No. 8
Laboratoire de Bactériologie,
Faculté de Médecine, 63001 Clermont-Ferrand
Cedex,1 and UMR 175, CNRS-MNHN, 29000 Quimper,3 France, and Setor de
Bacteriologia, Laboratório Lâmina LTDA, 71 - Botafogo,
Rio de Janeiro, Brazil 22280-0302
Received 28 November 2000/Returned for modification 19 March
2001/Accepted 11 May 2001
Three clinical strains (Escherichia coli Rio-6,
E. coli Rio-7, and Enterobacter cloacae Rio-9)
collected in 1996 and 1999 from hospitals in Rio de Janeiro (Brazil)
were resistant to broad-spectrum cephalosporins and gave a positive
double-disk synergy test. Two blaCTX-M genes
encoding The first extended-spectrum
The CTX-M enzymes form a rapidly growing family that comprises 11 enzymes, of which 8 have been described in the last 3 years. The CTX-M
enzymes have been subclassified by amino acid sequence similarities
into four groups (9). The first group contains enzymes
CTX-M-1 (MEN-1) (3, 5) and CTX-M-3 (17); the
second group contains the enzymes CTX-M-2 (6), Toho-1
(20), CTX-M-4 (14, 16), CTX-M-5
(11), CTX-M-6 (15), and CTX-M-7
(15) (previously designated CTX-M-5); and the third and
fourth groups contain CTX-M-8 (9) and Toho-2, respectively
(25). E. coli strains producing CTX-M-9 and
CTX-M-10, which are related to Toho-2 and CTX-M-3, respectively, were
recently reported in Spain (33; A. Oliver, J. C. Pérez-Díaz, T. M. Coque, F. Baquero, and R. Cantón, Abstr. 40th Intersci. Conf. Antimicrob. Agents
Chemother., abstr. 1480, p. 99, 2000).
The CTX-M-type enzymes are much more active against cefotaxime than
against ceftazidime and aztreonam. The amino acid residues critical for their extended-spectrum activity are partially known. Ser-237 and Arg-276 seem to be involved in the cefotaxime-hydrolyzing activity of CTX-M enzymes, but mutagenesis experiments of these residues led to only slight changes in their catalytic activities (14, 16). The extended-spectrum activity of
CTX-M-type To estimate the diversity of ESBLs in Brazil, clinical strains that
exhibited ESBL phenotypes in different species were collected from
hospitals in Rio de Janeiro in 1996 and 1999. We report three CTX-M-producing strains isolated in Brazil: two producing CTX-M-9 and
one producing a novel Asp-240 Clinical strains.
Table 1
shows the clinical strains and the plasmids used in this study. Three
clinical strains were isolated from three different patients
hospitalized in 1996 (Rio-6 and Rio-7) and in 1999 (Rio-9) of distinct
private hospitals of Rio de Janeiro, Brazil. E. coli strain
MEN producing CTX-M-1 (3) was used to synthesize the CTX-M
probe.
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.8.2269-2275.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Novel Cefotaximase (CTX-M-16) with Increased
Catalytic Efficiency Due to Substitution Asp-240
Gly
ABSTRACT
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
-lactamases of pl 7.9 and 8.2 were implicated in this
resistance: the blaCTX-M-9 gene observed in
E. coli Rio-7 and E. cloacae Rio-9 and a novel
CTX-M-encoding gene, designated blaCTX-M-16,
observed in E. coli strain Rio-6. The deduced amino acid
sequence of CTX-M-16 differed from CTX-M-9 only by the substitution Asp-240
Gly. The CTX-M-16-producing E. coli transformant
exhibited the same level of resistance to cefotaxime (MIC, 16 µg/ml)
but had a higher MIC of ceftazidime (MIC, 8 versus 1 µg/ml) than the CTX-M-9-producing transformant. Enzymatic studies revealed that CTX-M-16 had a 13-fold higher affinity for aztreonam and a 7.5-fold higher kcat for ceftazidime than CTX-M-9, thereby showing
that the residue in position 240 can modulate the enzymatic properties of CTX-M enzymes. The two blaCTX-M-9 genes and
the blaCTX-M-16 gene were located on different
plasmids, suggesting the presence of mobile elements associated with
CTX-M-encoding genes. CTX-M-2 and CTX-M-8 enzymes were found in Brazil
in 1996, and two other CTX-M -lactamases, CTX-M-9 and CTX-M-16, were
subsequently observed. These reports are evidence of the diversity of
CTX-M-type extended-spectrum -lactamases in Brazil.
INTRODUCTION
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
-lactamase (ESBL) of the CTX-M type (MEN-1, CTX-M-1) was reported at
the beginning of the 1990s (3, 5). Initially found in
Europe, CTX-M-producing strains have now been observed over a wide
geographic area including the Near East (6), Far East
(20, 25, 37), South America (4, 6; M. Galas, F. Pasteran, R. Melano, A. Petroni, G. Lopez, A. Corso, A. Rossi, and
WHONET Collaborative Group, Abstr. 38th Intersci. Conf.
Antimicrob. Agents Chemother., abstr. E-109, p. 201, 1998), and
Europe (3, 5, 14-17, 33). CTX-M enzymes have been
observed in different species of the family Enterobacteriaceae:
Escherichia coli (3, 5, 20, 25, 37), Salmonella
enterica serovar Typhimurium (4, 15, 16),
Klebsiella pneumoniae (6), Proteus
mirabilis (6, 9), Citrobacter freundii
(6, 17), Citrobacter amalonaticus
(9), Enterobacter aerogenes
(9), and Enterobacter cloacae (9),
and in the species Vibrio cholerae E1 Tor (M. Galas, A. Petroni, R. Melano, A. Corso, M. Rodriguez, M. L. Cacace, A. Bru,
and A. Rossi, Abstr. 38th Intersci. Conf. Antimicrob. Agents
Chemother. abstr. C-174, p. 119, 1998).
-lactamases seems therefore to be an
"intrinsic" enzymatic property of these ESBLs and not the
result of a few point mutations (14-16, 19).
Gly variant of CTX-M-9, designated CTX-M-16.
MATERIALS AND METHODS
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
TABLE 1.
Clinical strains from Rio de Janeiro (Brazil) and
recombinant plasmids used in the study
Mating-out assays. Direct transfers of plasmids harboring bla genes were performed by mating donor strains with in vitro-obtained rifampin- or nalidixic acid-resistant mutants of E. coli HB101 (34) as recipient strains, at 37°C on solid Mueller-Hinton medium. Transconjugants were selected on Mueller-Hinton agar containing rifampin (300 µg/ml) or nalidixic acid (150 µg/ml) and cefotaxime (2 µg/ml).
Susceptibility to -lactams.
MICs were determined by a
dilution method on Mueller-Hinton agar (Sanofi Diagnostics Pasteur,
Marnes la Coquette, France) with an inoculum of 104 CFU per
spot. Antibiotics were provided as powders by SmithKline Beecham
Pharmaceuticals (clavulanate), Lederle Laboratories (tazobactam), Eli
Lilly, Paris, France (cephalothin), Roussel-Uelaf (cefotaxime, cefpirome), Glaxo Wellcome Research and Development (ceftazidime), and
Bristol-Myers Squibb (aztreonam).
Isoelectric focusing.
Isoelectric focusing was performed
with polyacrylamide gels containing ampholines with a pH range of 3.5 to 10 as previously described (8). Visualization of
-lactamase activity was carried out with an agarose overlay
containing 6% (wt/vol) potassium iodide, 0.6% (wt/vol) iodine, and
0.6% (wt/vol) -lactam substrate: penicillin G to show overall
-lactamase content or cefotaxime to show the cefotaxime-hydrolyzing
-lactamases. -lactamases of known pIs were used as standards:
TEM-1 (pI 5.4), TEM-3 (pI 6.3), TEM-24 (pI 6.5), SHV-1 (pI 7.6), P99
(pI 7.8), and SHV-5 (pI 8.2).
-Lactamase preparation.
CTX-M-producing E. coli DH5
(pCIRio-6 and pCIRio-7) were grown in 6 liters of
brain heart infusion broth containing cefotaxime at 2 µg/ml for
18 h at 37°C. The bacteria collected by centrifugation were
suspended with 20 mM morpholineethane sulfonic acid (MES)-NaOH (pH 6.0)
and disrupted by ultrasonic treatment (four times for 30 s, each
time at 20 W). After centrifugation (10,000 × g for 10 min at 4°C), nucleic acids were precipitated by addition of 0.2 M
(7% [vol/vol]) spermine and centrifugation at 48,000 × g for 60 min at 4°C. The clarified supernatant was dialyzed
overnight against 20 mM MES-NaOH (pH 6.0). The CTX-M purification was
carried out as previously described (8) by ion-exchange
chromatography with an SP Sepharose column (Amersham Pharmacia
Biotech) and gel-filtration chromatography with a Superose 12 column
(Amersham Pharmacia Biotech). The total protein concentration was
estimated by the Bio-Rad protein assay (Bio-Rad, Richmond, Calif.),
with bovine serum albumin (Sigma Chemical Co., St. Louis, Mo.)
used as a standard.
-lactamase activity were performed as previously described
(8) with renaturation buffer {Tris-HCI (100 mM), Triton
X-100 (2% [vol/vol]), pH 7.0} and 0.5 mM nitrocephin (Oxoid,
Paris, France) in 100 mM phosphate buffer (pH 7.0), respectively.
Determination of -lactamase kinetic constants.
The
kinetic constants Km and
Kcat of the -lactamases were obtained by
computerized microacidimetric method as previously described
(24). The concentrations of the inhibitors (clavulanate and tazobactam) required to inhibit enzyme activity by 50%
(IC50s) were determined as described previously with
penicillin G (7). The specific activities,
IC50, and Ki values were determined
with penicillin G (200 mM) as the reporter substrate. The kinetic
constants were determined three times. The variation coefficients had a maximum of 25%, except with the CTX-M-9 enzyme for aztreonam and ceftazidime, for which the maximum was 40%.
PCR of CTX-M genes. The detection of CTX-M-1-, CTX-M-2-, and CTX-M-9-like-encoding genes and the synthesis of CTX-M probe were performed with the primers CTX-MA (5'-CGCTTTGCGATGTGCAG-3') and CTX-MB (5'-ACCGCGATATCGTTGGT-3') (temperature of annealing, 54°C), which correspond to conserved regions of CTX-M-type genes. An internal fragment of 550 pb was amplified from positions 264 to 814 (blaCTX-M-1 numbering). The complete open reading frames of blaCTX-M-9-like genes were amplified with the primers CTX-M-9A (5'-CTGATGTAACACGGATTGAC-3') and CTX-M-9C (5'-AGCGCCCCATTATTGAGAG-3'), which were located in the flanked sequences of blaCTX-M-9 (temperature of annealing, 54°C).
Plasmid extraction and hybridization. Plasmid DNAs were extracted by the method of Kado and Liu (22). The plasmid size was determined by comparison with plasmids Rsa (39 kb), TP114 (61 kb), pCFF04 (85 kb), and pCFF14 (180 kb) (7).
DNA probes used for hybridization were PCR products obtained with the primers CTX-MA and CTX-MB. Labeling was performed by random priming with a 2,4-dinitrophenol DNA labeling kit purchased from Appligene Oncor (Illkirch, France). Hybridization and revelation were performed with a DNP-DNA chemiluminescence detection kit (Appligene Oncor) according to the manufacturer's recommendations for DNA extracts denatured and immobilized on Nytran Filters.-Lactamase gene cloning.
The recombinant DNA
manipulations were performed as described by Sambrook et al.
(34). T4 DNA ligase was purchased from Boehringer,
Mannheim, Germany. The CTX-M-encoding sequence was cloned as follows.
PCR products, which were obtained with proofreading Taq
polymerase Tfu (Appligene Oncor) and the primers CTX-M-9A and CTX-M-9C, were ligated in the SmaI site of the phagemid
pBK-CMV (Stratagene, La Jolla, Calif.). E. coli DH5
(34) was transformed by electroporation. The transformants
harboring the recombinant CTX-M-encoding plasmids were selected on
Mueller-Hinton agar supplemented with 2 µg of cefotaxime per ml.
DNA sequencing. The sequences were determined by direct sequencing of PCR products, performed by the dideoxy chain termination procedure of Sanger et al. (35) on an ABI 1377 automatic sequencer using the ABI PRISM Dye Terminator Cycle Sequencing Ready Reaction kit with AmpliTaq DNA polymerase FS (Perkin-Elmer/Applied Biosystems, Foster City, Calif.).
Computer analysis. The nucleotide sequence and the deduced protein sequence were analyzed with the software available over the Internet at the National Center for Biotechnology Information. Hydrophobic blotting was performed using the method of Nielsen et al. (27). Multiple sequence alignment and pairwise comparisons of sequences were carried out with the help of ClustalW Software (version 1.74) (36). Twelve class A CTX-M enzymes were compared to CTX-M-16: CTX-M-1, CTX-M-2, Toho-1, CTX-M-3, CTX-M-4, CTX-M-5, CTX-M-6, CTX-M-7, CTX-M-8, CTX-M-9, CTX-M-10, and Toho-2. Phylogenetic analysis was performed by the neighbor-joining method using PHYLIP (Phylogeny Inference Package, version 3.5c) from a distance matrix, which was carried out with the Dayhoff PAM matrix (13).
Nucleotide sequence accession number. The blaCTX-M-16nucleotide sequence data appear in the GenBank nucleotide sequence database under accession number AY029068.
| |
RESULTS |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
|
|---|
Characterization of clinical isolates.
The clinical isolates
Rio-6, Rio-7, and Rio-9 exhibited resistance to broad-spectrum
cephalosporins (MICs: cefotaxime, 16 to 128 µg/ml; ceftazidime, 32 to
256 µg/ml; aztreonam, 64 to 128 µg/ml) and a positive double-disk
synergy test. Isoelectric point determination with penicillin G as
substrate revealed the presence of two to three different
-lactamases per strain (Table 1), but using cefotaxime as substrate,
only one enzyme, of pI 7.9 in strains Rio-7 and Rio-9 or of pI 8.2 in
strain Rio-6, showed a strong cefotaxime-hydrolyzing activity. The
three strains exhibited a positive amplification with the primers
CTX-MA and CTX-MB, which were designated from conserved sequences of
blaCTX-M genes. These results suggested the
presence of two distinct blaCTX-M genes which
encoded enzymes of pI 8.2 in strain Rio-6 and of pI 7.9 in strains
Rio-7 and Rio-9.
Plasmid content and transfer of -lactam resistance.
Transconjugants were obtained from E. coli Rio-6 and
E. cloacae Rio-9. They produced cefotaxime-hydrolyzing
-lactamases of alkaline pI (8.2 or 7.9) and associated with a
-lactamase of pI 5.4, which was identified by PCR and sequencing as
the TEM-1 penicillinase.
|
DNA sequencing.
DNA sequencing of PCR products obtained with
primers CTX-M-9A and CTX-M-9C revealed that strains Rio-7 and Rio-9
contained the gene blaCTX-M-9, previously
reported in an E. coli strain isolated in Spain
(33), whereas strain Rio-6 harbored a new gene,
designated blaCTX-M-16, which differed
from blaCTX-M-9 by the mutation AG at
position 725.
Gly in position
240 (Fig. 2). The strain Rio-6 thus
produced a novel CTX-M-type enzyme, which was
designated CTX-M-16.
|
|
Cloning of the -lactamase gene.
The coding sequences of
CTX-M-9 and CTX-M-16, obtained by PCR with primers CTX-M-9A and
CTX-M-9B, were cloned downstream of the LacZ promoter of
plasmid pBK-CMV. The obtained recombinant plasmids were designated
pCPRio-6 and pCPRio-7 and contained a 0.9-kb insert encoding the
enzymes CTX-M-16 and CTX-M-9, respectively.
-Lactam susceptibility.
MICs of -lactams for the
E. coli DH5 tranformants producing CTX-M-9 (pCPRio-7) and
CTX-M-16 (pCPRio-6) are listed in Table 2. These CTX-M-producing strains
exhibited a high level of resistance to amino- and carboxypenicillins
(MICs, >2,048 µg/ml), piperacillin (MIC, 256 µg/ml), and
cephalothin and cefuroxime (MICs, 512 µg/ml). The similar level of
resistance to cefotaxime (MIC, 16 µg/ml) and aztreonam (MICs, 4 to 8 µg/ml) was observed with CTX-M-16 and CTX-M-9 producers, while the
MICs of ceftazidime were higher for CTX-M-16 producers than for CTX-M-9
producers (MICs, 8 versus 1 µg/ml).
|
-lactams. All strains were susceptible to associations of
clavulanate or tazobactam and broad-spectrum cephalosporins (MICs, 0.06 to 0.25 µg/ml).
Biochemical properties of the -lactamase CTX-M-16.
The
purified proteins appeared on SDS-polyacrylamide gels as a band of 28.6 kDa for CTX-M-16 (Fig. 4) and CTX-M-9
(data not shown). The specific activities of purified (
97% pure)
CTX-M-16 and CTX-M-9 were 140 and 615 µmol · min
1 · mg of protein1, respectively,
with 200 mM penicillin G as the substrate.
|
1) was found than for ceftazidime (2 to 15 s1) and aztreonam (10 to 3 s1).
|
-lactams,
particularly for aztreonam, since the binding of this substrate was
13-fold higher for CTX-M-16 than for CTX-M-9. Conversely, CTX-M-9 had
higher Kcat values than CTX-M-16 with all
substrates except cefuroxime and particularly for cefotaxime and
ceftazidime, for which kcat values were higher for CTX-M-16 than for CTX-M-9.
CTX-M-9 and CTX-M-16 were susceptible to tazobactam (IC50s,
0.036 and 0.030 µM, respectively), clavulanate (IC50s,
0.007 and 0.008 µM, respectively), and to a lesser extent to
sulbactam (IC50s, 3.0 and 4.5 µM, respectively).
| |
DISCUSSION |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
|
|---|
The starting point of this work was the observation of three clinical strains isolated in Brazil, E. coli Rio-6 (isolated from urine of a patient hospitalized in a home care unit) and E. coli Rio-7 and E. cloacae Rio-9 (isolated from tracheal aspirations of patients hospitalized in an intensive care unit), that exhibited resistance to broad-spectrum cephalosporins with a positive double-disk synergy test. Two different CTX-M-encoding genes were implicated in this resistance phenotype: the novel CTX-M-encoding gene blaCTX-M-16, which was related to blaCTX-M-9 and was observed in E. coli strain Rio-6, and the blaCTX-M-9 gene (33) in strains E. coli Rio-7 and E. cloacae Rio-9.
The blaCTX-M-16 gene is probably the result of a
point mutation of the blaCTX-M-9 gene, because
the two genes were characterized in the same geographic area and
differed by one nucleotide only. blaCTX-M-16 and the closely related gene
blaToho-2 were observed at almost the same
time, in Spain and Japan, respectively (25, 33). The
concurrent emergence of these blaCTX-M-9-type
genes in two geographic areas widely separated could be explained by their transfer from widespread environmental strains, as previously observed with the gene blaSFO-1, which was
probably transferred from Serratia fonticola to E. cloacae (26). The most closely related enzymes to
CTX-M genes are the chromosome-encoded enzymes of Klebsiella
oxytoca (2, 32), Serratia fonticola
(28), Citrobacter diversus (30),
and Proteus vulgaris (29), but there is no
direct phylogenetic connection between these -lactamases and CTX-M
enzymes. In addition, blaCTX-M-2-like genes have
been observed in the chromosome of K. ascorbata (A. Philippon, Abstr. 39th Intersci. Conf. Antimicrob. Agents
Chemother., abstr 2044a, 1999), which therefore is a potential
reservoir for a CTX-M-encoding gene. However, the CTX-M-9 and CTX-M-16
enzymes are distantly related to the CTX-M-2-like -lactamases and
hence could originate from variant genes present in the same species or
in related species. The two blaCTX-M-9 genes and
the blaCTX-M-16 gene, like
blaCTX-M-8 and blaCTX-M-3
(9, 17), were located on different plasmids. This suggests
that mobile elements associated with CTX-M-encoding genes are present
and that they could be involved in gene transfers.
The phylogenetic relations between the enzymes reported in the CTX-M family show four types of CTX-M enzymes-CTX-M-1 type, which includes CTX-M-1, CTX-M-3, and CTX-M-10; CTX-M-2 type, which includes CTX-M-2, Toho-1, CTX-M-4, CTX-M-5, CTX-M-6, and CTX-M-7; CTX-M-8 type, which has only one member; and CTX-M-9 (or Toho-2) type, which includes Toho-2, CTX-M-9, and the novel enzyme CTX-M-16.
The catalytic properties of CTX-M-9 and CTX-M-16 have similarities with
those of previously reported CTX-M enzymes, such as higher catalytic
activity against cefotaxime than against ceftazidime and aztreonam. The
enzymes CTX-M-9 and CTX-M-16 include the amino acid residues Ser-237,
Phe-160, Gly-232, and Arg-276, which are thought to play a part in the
cefotaxime-hydrolyzing activity of CTX-M enzymes (3, 14-16, 19,
20, 25). In addition, the CTX-M-9 and CTX-M-16 -lactamases
are susceptible to inhibitors, and in particular to tazobactam, as
reported elsewhere (9, 15, 16, 25).
The residue in position 240 is not conserved among -lactamases of
class A. At least three types of residue are observed at this position:
(i) acid residues (Glu or Asp) in TEM and SHV-1 penicillinases, as well
as in CTX-M ESBLs and their closely related enzymes; (ii) a Lys residue
in some SHV- and TEM-type ESBLs; (iii) a Gly residue in
carboxypenicillinases and in the ESBLs PER, VEB-1, and BES-1 (8,
31). CTX-M-16 is the first CTX-M-type ESBL which harbors the
substitution Asp-240Gly. This substitution increased the binding of
aztreonam (13-fold), as well as the kcat against
ceftazidime (7.5-fold) and to a lesser extent that against cefotaxime
(3-fold). The cefotaximase BES-1, which harbors the same Gly residue in
position 240, exhibits the same behavior against aztreonam, cefotaxime,
and ceftazidime as does CTX-M-16 (8). The ESBL PER-1,
which has a good catalytic efficiency against cefotaxime and
ceftazidime, also contains a Gly-240 residue. Bouthors et al.
(10) showed that the substitution Gly-240Glu of PER-1 causes a reduction of affinity for aztreonam (around fourfold) and a
decrease in catalytic activity against cefotaxime and ceftazidime (around twofold and threefold, respectively).
Residues Lys-240 and Arg-240 are known to play a major role in the
extended-spectrum activity of TEM- and SHV-type ESBLs. They lead
to an increase in hydrolyzing activities against ceftazidime and
aztreonam but are not involved in cefotaxime-hydrolyzing activity. Lys
and Arg are positively-charged residues which can form an electrostatic bond with the carboxylic acid group on oximino
substituents of aztreonam and ceftazidime (23) and induce
a rotation of the aminothiazole-oxime group (18). They
could therefore remove the obstruction caused by the bulky
t-carbon group of the oxime and allow hydrogen bonding of
the acylamide NH to the 3-strand of the enzyme (18).
Thus, Lys and Arg in position 240 favor carboxy oximino -lactam
bonding and hydrolyzing. Residue Gly-240, which has no side chain, is
not able to form electrostatic interactions with -lactams. However,
the absence of a side chain in position 240 could facilitate the
positioning of the aminothiazole-oxime group of cefotaxime,
aztreonam, and ceftazidime in the catalytic pocket.
In contrast with cefotaxime- and ceftazidime-hydrolyzing activities,
aztreonam-hydrolyzing activity was not modified by the residue Gly-240.
The sulfonic acid group of aztreonam may form weaker interactions with
the side chains of residues Ser-130, Lys-234, Thr-235, and Arg-276 of
the CTX-M -lactamases than does the functionally equivalent
carboxylate group of cefotaxime and ceftazidime (12).
Thus, the weak interaction of aztreonam with CTX-M-16 may alter its
positioning in its catalytic pocket, resulting in a weak
aztreonam-hydrolyzing activity. It is likely therefore that aztreonam,
unlike cefotaxime and ceftazidime, requires the electrostatic
interaction mediated by the positively-charged residues in position 240 for correct positioning and, hence, for hydrolysis. However, the
Asp-240Lys substitution would require two mutations in the
corresponding codon and thus is a more improbable spontaneous genetic
event than the single mutation observed in the CTX-M-16 enzyme.
Since the first report of MEN-1 (CTX-M-1) a decade ago (3, 5), a great variety of CTX-M enzymes have been observed. In a previous study, we reported CTX-M-2- and CTX-M-8-producing Enterobacteriaceae isolated in Brazil (9), and in this work we report CTX-M-9- and CTX-M-16-producing Enterobacteriaceae. These findings show the spread, diversity, and implantation of CTX-M enzymes in Brazil. CTX-M-2 was first characterized in Argentina, and Galas et al. reported that the predominant ESBL in the country is CTX-M-2 (M. Galas et al., 38th ICAAC, abstr. E-109). Like Eastern Europe and Japan (14-17, 37), South America is an important source of CTX-M-producing bacteria.
| |
ACKNOWLEDGMENTS |
|---|
We thank Rolande Perroux, Marlène Jan, and Dominique Rubio for technical assistance. We are also grateful to Ferran Navarro, Department de Microbiologia, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma Barcelona (Barcelona, Spain), for the flanked sequences of blaCTX-M-9 and to Bio-Merieux for the transport of strains from Brazil.
This work was supported in part by a grant from Ministère de l'Education Nationale, de la Recherche et de la Technologie.
| |
FOOTNOTES |
|---|
* Corresponding author. Mailing address: Faculté de Médecine, Service de Bactériologie-Virologie, 28, Place Henri Dunant, 63 001 Clermont-Ferrand Cedex, France. Phone: 33 4 73 60 80 18. Fax: 33 4 73 27 74 94. E-mail: Richard.Bonnet{at}u-clermont1.fr.
| |
REFERENCES |
|---|
|
Top
Abstract
Introduction
Materials and Methods
Results
Discussion
References
|
|---|
| 1. |
Ambler, R. P.,
A. F. W. Coulson,
J.-M. Frére,
J. M. Ghuysen,
B. Joris,
M. Forsman,
R. C. Lévesque,
G. Tiraby, and S. G. Waley.
1991.
A standard numbering scheme for the class A -lactamases.
Biochem. J.
276:269-272.
|
| 2. |
Arakawa, Y.,
M. Ohta,
N. Kido,
M. Mori,
H. Ito,
T. Komatsu,
Y. Fujii, and N. Kato.
1989.
Chromosomal -lactamase of Klebsiella oxytoca, a new class A enzyme that hydrolyzes broad-spectrum -lactam antibiotics.
Antimicrob. Agents Chemother.
33:63-70 |
| 3. |
Barthélémy, M.,
J. Péduzzi,
H. Bernard,
C. Tancrede, and R. Labia.
1992.
Close amino acid sequence relationship between the new plasmid-mediated extended-spectrum -lactamase MEN-1 and chromosomally encoded enzymes of Klebsiella oxytoca.
Biochim. Biophys. Acta
1122:15-22[CrossRef][Medline].
|
| 4. | Bauernfeind, A., J. M. Casellas, M. Goldberg, M. Holley, R. Jungwirth, P. Mangold, T. Rohnisch, S. Schweighart, and R. Wilhelm. 1992. A new plasmidic cefotaximase from patients infected with Salmonella typhimurium. Infection 20:158-163[CrossRef][Medline]. |
| 5. | Bauernfeind, A., H. Grimm, and S. Schweighart. 1990. A new plasmidic cefotaximase in a clinical isolate of Escherichia coli. Infection 18:294-298[CrossRef][Medline]. |
| 6. |
Bauernfeind, A.,
I. Stemplinger,
R. Jungwirth,
S. Ernst, and J. M. Casellas.
1996.
Sequences of -lactamase genes encoding CTX-M-1 (MEN-1) and CTX-M-2 and relationship of their amino acid sequences with those of other -lactamases.
Antimicrob. Agents Chemother.
40:509-513[Abstract].
|
| 7. |
Bonnet, R.,
C. De Champs,
D. Sirot,
C. Chanal,
R. Labia, and J. Sirot.
1999.
Diversity of TEM mutants in Proteus mirabilis.
Antimicrob. Agents Chemother.
43:2671-2677 |
| 8. |
Bonnet, R.,
J. L. M. Sampaio,
C. Chanal,
D. Sirot,
C. De Champs,
J. L. Viallard,
R. Labia, and J. Sirot.
2000.
A novel class A extended-spectrum -lactamase (BES-1) in Serratia marcescens isolated in Brazil.
Antimicrob. Agents Chemother.
44:3061-3068 |
| 9. |
Bonnet, R.,
J. L. M. Sampaio,
R. Labia,
C. De Champs,
D. Sirot,
C. Chanal, and J. Sirot.
2000.
A novel CTX-M -lactamase (CTX-M-8) in cefotaxime-resistant Enterobacteriaceae isolated in Brazil.
Antimicrob. Agents Chemother.
44:1936-1942 |
| 10. |
Bouthors, A. T.,
N. Dagoneau-Blanchard,
T. Naas,
P. Nordmann,
V. Jarlier, and W. Sougakoff.
1998.
Role of residues 104, 164, 166, 238 and 240 in the substrate profile of PER-1 -lactamase hydrolysing third-generation cephalosporins.
Biochem. J.
330:1443-1449.
|
| 11. |
Bradford, P. A.,
Y. Yang,
D. Sahm,
I. Grope,
D. Gardovska, and G. Storch.
1998.
CTX-M-5, a novel cefotaxime-hydrolyzing -lactamase from an outbreak of Salmonella typhimurium in Latvia.
Antimicrob. Agents Chemother.
42:1980-1984 |
| 12. |
Cantu, C.,
W. Huang, and T. Palzkill.
1996.
Selection and characterization of amino acid substitutions at residues 237-240 of TEM-1 -lactamase with altered substrate specificity for aztreonam and ceftazidime.
J. Biol. Chem.
271:22538-22545 |
| 13. | Felsenstein, J. 1989. PHYLIP, phylogeny inference package, (version 3.2). Cladistics 5:164-166. |
| 14. |
Gazouli, M.,
N. J. Legakis, and L. S. Tzouvelekis.
1998.
Effect of substitution of Asn for Arg-276 in the cefotaxime-hydrolyzing class A -lactamase CTX-M-4.
FEMS Microbiol. Lett.
169:289-293[Medline].
|
| 15. |
Gazouli, M.,
E. Tzelepi,
A. Markogiannakis,
N. J. Legakis, and L. S. Tzouvelekis.
1998.
Two novel plasmid-mediated cefotaxime-hydrolyzing -lactamases (CTX-M-5 and CTX-M-6) from Salmonella typhimurium.
FEMS Microbiol. Lett.
165:289-293[Medline].
|
| 16. |
Gazouli, M.,
E. Tzelepi,
S. V. Sidorenko, and L. S. Tzouvelekis.
1998.
Sequence of the gene encoding a plasmid-mediated cefotaxime-hydrolyzing class A -lactamase (CTX-M-4): involvement of serine 237 in cephalosporin hydrolysis.
Antimicrob. Agents Chemother.
42:1259-1262 |
| 17. |
Gniadkowski, M.,
I. Schneider,
A. Palucha,
R. Jungwirth,
B. Mikiewicz, and A. Bauernfeind.
1998.
Cefotaxime-resistant Enterobacteriaceae isolates from a hospital in Warsaw, Poland: identification of a new CTX-M-3 cefotaxime-hydrolyzing -lactamase that is closely related to the CTX-M-1/MEN-1 enzyme.
Antimicrob. Agents Chemother.
42:827-832 |
| 18. |
Huletsky, A.,
J. R. Knox, and R. C. Levesque.
1993.
Role of Ser-238 and Lys-240 in the hydrolysis of third-generation cephalosporins by SHV-type -lactamases probed by site-directed mutagenesis and three-dimensional modeling.
J. Biol. Chem.
268:3690-3697 |
| 19. |
Ibuka, A.,
A. Taguchi,
M. Ishiguro,
S. Fushinobu,
Y. Ishii,
S. Kamitori,
K. Okuyama,
K. Yamaguchi,
M. Konno, and H. Matsuzawa.
1999.
Crystal structure of the E166A mutant of extended-spectrum -lactamase Toho-1 at 1.8 A resolution.
J. Mol. Biol.
285:2079-2087[CrossRef][Medline].
|
| 20. |
Ishii, Y.,
A. Ohno,
H. Taguchi,
S. Imajo,
M. Ishiguro, and H. Matsuzawa.
1995.
Cloning and sequence of the gene encoding a cefotaxime-hydrolyzing class A -lactamase isolated from Escherichia coli.
Antimicrob. Agents Chemother.
39:2269-2275[Abstract].
|
| 21. |
Jarlier, V.,
M. H. Nicolas,
G. Fournier, and A. Philippon.
1988.
Extended broad-spectrum -lactamases conferring transferable resistance to newer -lactam agents in Enterobacteriaceae: hospital prevalence and susceptibility patterns.
Rev. Infect. Dis.
10:867-878[Medline].
|
| 22. |
Kado, C. I., and L. Liu.
1981.
Rapid procedure for detection and isolation of large and small plasmids.
J. Bacteriol.
145:1365-1373 |
| 23. |
Knox, J. R.
1995.
Extended-spectrum and inhibitor-resistant TEM-type -lactamases: mutations, specificity, and three-dimensional structure.
Antimicrob. Agents Chemother.
39:2593-2601[Medline].
|
| 24. |
Labia, R.,
J. Andrillon, and F. Le Goffic.
1973.
Computerized microacidimetric determination of -lactamase Michaelis-Menten constants.
FEBS Lett.
33:42-44[CrossRef][Medline].
|
| 25. |
Ma, L.,
Y. Ishii,
M. Ishiguro,
H. Matsuzawa, and K. Yamaguchi.
1998.
Cloning and sequencing of the gene encoding Toho-2, a class A -lactamase preferentially inhibited by tazobactam.
Antimicrob. Agents Chemother.
42:1181-1186 |
| 26. |
Matsumoto, Y., and M. Inoue.
1999.
Characterization of SFO-1, a plasmid-mediated inducible class A beta-lactamase from Enterobacter cloacae.
Antimicrob. Agents Chemother.
43:307-313 |
| 27. |
Nielsen, H.,
J. Engelbrecht,
S. Brunak, and G. Von Heijne.
1997.
Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites.
Protein Eng.
10:1-6 |
| 28. | Péduzzi, J., S. Farzaneh, A. Reynaud, M. Barthélémy, and R. Labia. 1997. Characterization and amino acid sequence analysis of a new oxyimino cephalosporin-hydrolyzing class A beta-lactamase from Serratia fonticola CUV. Biochim. Biophys. Acta 1341:58-70[CrossRef][Medline]. |
| 29. |
Péduzzi, J.,
A. Reynaud,
P. Baron,
M. Barthélémy, and R. Labia.
1994.
Chromosomally encoded cephalosporin-hydrolyzing -lactamase of Proteus vulgaris R0104 belongs to Ambler's class A.
Biochim. Biophys. Acta
1207:31-39[CrossRef][Medline].
|
| 30. | Perilli, M. G., N. Franceschini, B. Segatore, G. Amicosante, A. Oratore, C. duez, B. Joris, and J. M. Frére. 1991. Cloning and nucleotide sequencing of the gene encoding the beta-lactamase from Citrobacter diversus. FEMS Microbiol. Lett. 67:79-84[CrossRef][Medline]. |
| 31. |
Poirel, L.,
T. Naas,
M. Guibert,
E. B. Chaibi,
R. Labia, and P. Nordmann.
1999.
Molecular and biochemical characterization of VEB-1, a novel class A extended-spectrum -lactamase encoded by an Escherichia coli integron gene.
Antimicrob. Agents Chemother.
43:573-581 |
| 32. |
Reynaud, A.,
J. Péduzzi,
M. Barthélémy, and R. Labia.
1991.
Cefotaxime-hydrolyzing activity of the -lactamase of Klebsiella oxytoca D488 could be related to a threonine residue at position 140.
FEMS Microbiol. Lett.
81:185-192[CrossRef].
|
| 33. |
Sadate, M.,
R. Tarrago,
F. Navarro,
E. Miro,
C. Verges,
J. Barbe, and G. Prats.
2000.
Cloning and sequence of the gene encoding a novel cefotaxime-hydrolyzing beta-lactamase (CTX-M-9) from Escherichia coli in Spain.
Antimicrob. Agents Chemother.
44:1970-1973 |
| 34. | Sambrook, J., E. F. Fritsch, and T. Maniatis. 1989. Molecular cloning: a laboratory manual, 2nd ed., vol. 1. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y. |
| 35. |
Sanger, F.,
S. Nicklen, and A. R. Coulson.
1977.
DNA sequencing with chain-terminating inhibitors.
Proc. Natl. Acad. Sci. USA
74:5463-5467 |
| 36. |
Thompson, J. D.,
D. G. Higgins, and T. J. Gibson.
1994.
CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.
Nucleic Acids Res.
22:4673-4680 |
| 37. |
Yagi, T.,
H. Kurokawa,
K. Senda,
S. Ichiyama,
H. Ito,
S. Ohsuka,
K. Shibayama,
K. Shimokata,
N. Kato,
M. Ohta, and Y. Arakawa.
1997.
Nosocomial spread of cephem-resistant Escherichia coli strains carrying multiple Toho-1-like -lactamase genes.
Antimicrob. Agents Chemother.
41:2606-2611[Abstract].
|
Antimicrobial Agents and Chemotherapy, August 2001, p. 2269-2275, Vol. 45, No. 8
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.8.2269-2275.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Yin, J., Cheng, J., Sun, Z., Ye, Y., Gao, Y.-F., Li, J.-B., Zhang, X.-J.
(2009). Characterization of two plasmid-encoded cefotaximases found in clinical Escherichia coli isolates: CTX-M-65 and a novel enzyme, CTX-M-87. J Med Microbiol
58: 811-815
[Abstract] [Full Text] -
Doublet, B., Granier, S. A., Robin, F., Bonnet, R., Fabre, L., Brisabois, A., Cloeckaert, A., Weill, F.-X.
(2009). Novel Plasmid-Encoded Ceftazidime-Hydrolyzing CTX-M-53 Extended-Spectrum {beta}-Lactamase from Salmonella enterica Serotypes Westhampton and Senftenberg. Antimicrob. Agents Chemother.
53: 1944-1951
[Abstract] [Full Text] -
Celenza, G., Luzi, C., Aschi, M., Segatore, B., Setacci, D., Pellegrini, C., Forcella, C., Amicosante, G., Perilli, M.
(2008). Natural D240G Toho-1 mutant conferring resistance to ceftazidime: biochemical characterization of CTX-M-43. J Antimicrob Chemother
62: 991-997
[Abstract] [Full Text] -
Mendonca, N., Manageiro, V., Robin, F., Salgado, M. J., Ferreira, E., Canica, M., Bonnet, R.
(2008). The Lys234Arg Substitution in the Enzyme SHV-72 Is a Determinant for Resistance to Clavulanic Acid Inhibition. Antimicrob. Agents Chemother.
52: 1806-1811
[Abstract] [Full Text] -
Brasme, L., Nordmann, P., Fidel, F., Lartigue, M. F., Bajolet, O., Poirel, L., Forte, D., Vernet-Garnier, V., Madoux, J., Reveil, J. C., Alba-Sauviat, C., Baudinat, I., Bineau, P., Bouquigny-Saison, C., Eloy, C., Lafaurie, C., Simeon, D., Verquin, J. P., Noel, F., Strady, C., De Champs, C.
(2007). Incidence of class A extended-spectrum {beta}-lactamases in Champagne-Ardenne (France): a 1 year prospective study. J Antimicrob Chemother
60: 956-964
[Abstract] [Full Text] -
Fernandez, A., Gil, E., Cartelle, M., Perez, A., Beceiro, A., Mallo, S., Tomas, M. M., Perez-Llarena, F. J., Villanueva, R., Bou, G.
(2007). Interspecies spread of CTX-M-32 extended-spectrum {beta}-lactamase and the role of the insertion sequence IS1 in down-regulating blaCTX-M gene expression. J Antimicrob Chemother
59: 841-847
[Abstract] [Full Text] -
Lavigne, J.-P., Marchandin, H., Delmas, J., Moreau, J., Bouziges, N., Lecaillon, E., Cavalie, L., Jean-Pierre, H., Bonnet, R., Sotto, A.
(2007). CTX-M {beta}-Lactamase-Producing Escherichia coli in French Hospitals: Prevalence, Molecular Epidemiology, and Risk Factors. J. Clin. Microbiol.
45: 620-626
[Abstract] [Full Text] -
Tofteland, S., Haldorsen, B., Dahl, K. H., Simonsen, G. S., Steinbakk, M., Walsh, T. R., Sundsfjord, A., the Norwegian ESBL Study Group,
(2007). Effects of Phenotype and Genotype on Methods for Detection of Extended-Spectrum-{beta}-Lactamase-Producing Clinical Isolates of Escherichia coli and Klebsiella pneumoniae in Norway. J. Clin. Microbiol.
45: 199-205
[Abstract] [Full Text] -
Bae, I. K., Lee, Y.-N., Hwang, H. Y., Jeong, S. H., Lee, S. J., Kwak, H.-S., Song, W., Kim, H. J., Youn, H.
(2006). Emergence of CTX-M-12 extended-spectrum {beta}-lactamase-producing Escherichia coli in Korea. J Antimicrob Chemother
58: 1257-1259
[Abstract] [Full Text] -
Lavigne, J.-P., Marchandin, H., Delmas, J., Bouziges, N., Lecaillon, E., Cavalie, L., Jean-Pierre, H., Bonnet, R., Sotto, A.
(2006). qnrA in CTX-M-Producing Escherichia coli Isolates from France. Antimicrob. Agents Chemother.
50: 4224-4228
[Abstract] [Full Text] -
al Naiemi, N., Duim, B., Bart, A.
(2006). A CTX-M extended-spectrum {beta}-lactamase in Pseudomonas aeruginosa and Stenotrophomonas maltophilia.. J Med Microbiol
55: 1607-1608
[Full Text] -
Bae, I. K., Lee, B. H., Hwang, H. Y., Jeong, S. H., Hong, S. G., Chang, C. L., Kwak, H.-S., Kim, H. J., Youn, H.
(2006). A novel ceftazidime-hydrolysing extended-spectrum {beta}-lactamase, CTX-M-54, with a single amino acid substitution at position 167 in the omega loop. J Antimicrob Chemother
58: 315-319
[Abstract] [Full Text] -
Delmas, J., Robin, F., Carvalho, F., Mongaret, C., Bonnet, R.
(2006). Prediction of the Evolution of Ceftazidime Resistance in Extended-Spectrum {beta}-Lactamase CTX-M-9. Antimicrob. Agents Chemother.
50: 731-738
[Abstract] [Full Text] -
Paterson, D. L., Bonomo, R. A.
(2005). Extended-Spectrum {beta}-Lactamases: a Clinical Update. Clin. Microbiol. Rev.
18: 657-686
[Abstract] [Full Text] -
Moubareck, C., Daoud, Z., Hakime, N. I., Hamze, M., Mangeney, N., Matta, H., Mokhbat, J. E., Rohban, R., Sarkis, D. K., Doucet-Populaire, F.
(2005). Countrywide Spread of Community- and Hospital-Acquired Extended-Spectrum {beta}-Lactamase (CTX-M-15)-Producing Enterobacteriaceae in Lebanon. J. Clin. Microbiol.
43: 3309-3313
[Abstract] [Full Text] -
Lee, S., Park, Y.-J., Kim, M., Lee, H. K., Han, K., Kang, C. S., Kang, M. W.
(2005). Prevalence of Ambler class A and D {beta}-lactamases among clinical isolates of Pseudomonas aeruginosa in Korea. J Antimicrob Chemother
56: 122-127
[Abstract] [Full Text] -
Carattoli, A., Lovari, S., Franco, A., Cordaro, G., Di Matteo, P., Battisti, A.
(2005). Extended-Spectrum {beta}-Lactamases in Escherichia coli Isolated from Dogs and Cats in Rome, Italy, from 2001 to 2003. Antimicrob. Agents Chemother.
49: 833-835
[Abstract] [Full Text] -
Munday, C. J., Boyd, D. A., Brenwald, N., Miller, M., Andrews, J. M., Wise, R., Mulvey, M. R., Hawkey, P. M.
(2004). Molecular and Kinetic Comparison of the Novel Extended-Spectrum {beta}-Lactamases CTX-M-25 and CTX-M-26. Antimicrob. Agents Chemother.
48: 4829-4834
[Abstract] [Full Text] -
Pitout, J. D. D., Hossain, A., Hanson, N. D.
(2004). Phenotypic and Molecular Detection of CTX-M-{beta}-Lactamases Produced by Escherichia coli and Klebsiella spp.. J. Clin. Microbiol.
42: 5715-5721
[Abstract] [Full Text] -
Weill, F.-X., Lailler, R., Praud, K., Kerouanton, A., Fabre, L., Brisabois, A., Grimont, P. A. D., Cloeckaert, A.
(2004). Emergence of Extended-Spectrum-{beta}-Lactamase (CTX-M-9)-Producing Multiresistant Strains of Salmonella enterica Serotype Virchow in Poultry and Humans in France. J. Clin. Microbiol.
42: 5767-5773
[Abstract] [Full Text] -
Boyd, D. A., Tyler, S., Christianson, S., McGeer, A., Muller, M. P., Willey, B. M., Bryce, E., Gardam, M., Nordmann, P., Mulvey, M. R.
(2004). Complete Nucleotide Sequence of a 92-Kilobase Plasmid Harboring the CTX-M-15 Extended-Spectrum Beta-Lactamase Involved in an Outbreak in Long-Term-Care Facilities in Toronto, Canada. Antimicrob. Agents Chemother.
48: 3758-3764
[Abstract] [Full Text] -
De Champs, C., Chanal, C., Sirot, D., Baraduc, R., Romaszko, J. P., Bonnet, R., Plaidy, A., Boyer, M., Carroy, E., Gbadamassi, M. C., Laluque, S., Oules, O., Poupart, M. C., Villemain, M., Sirot, J.
(2004). Frequency and diversity of Class A extended-spectrum {beta}-lactamases in hospitals of the Auvergne, France: a 2 year prospective study. J Antimicrob Chemother
54: 634-639
[Abstract] [Full Text] -
Sturenburg, E., Kuhn, A., Mack, D., Laufs, R.
(2004). A novel extended-spectrum {beta}-lactamase CTX-M-23 with a P167T substitution in the active-site omega loop associated with ceftazidime resistance. J Antimicrob Chemother
54: 406-409
[Abstract] [Full Text] -
Cartelle, M., del Mar Tomas, M., Molina, F., Moure, R., Villanueva, R., Bou, G.
(2004). High-Level Resistance to Ceftazidime Conferred by a Novel Enzyme, CTX-M-32, Derived from CTX-M-1 through a Single Asp240-Gly Substitution. Antimicrob. Agents Chemother.
48: 2308-2313
[Abstract] [Full Text] -
Eckert, C., Gautier, V., Saladin-Allard, M., Hidri, N., Verdet, C., Ould-Hocine, Z., Barnaud, G., Delisle, F., Rossier, A., Lambert, T., Philippon, A., Arlet, G.
(2004). Dissemination of CTX-M-Type {beta}-Lactamases among Clinical Isolates of Enterobacteriaceae in Paris, France. Antimicrob. Agents Chemother.
48: 1249-1255
[Abstract] [Full Text] -
Villegas, M. V., Correa, A., Perez, F., Zuluaga, T., Radice, M., Gutkind, G., Casellas, J. M., Ayala, J., Lolans, K., Quinn, J. P., the Colombian Nosocomial Resistance Study Group,,
(2004). CTX-M-12 {beta}-Lactamase in a Klebsiella pneumoniae Clinical Isolate in Colombia. Antimicrob. Agents Chemother.
48: 629-631
[Abstract] [Full Text] -
Bonnet, R.
(2004). Growing Group of Extended-Spectrum {beta}-Lactamases: the CTX-M Enzymes. Antimicrob. Agents Chemother.
48: 1-14
[Full Text] -
Schwaber, M. J., Raney, P. M., Rasheed, J. K., Biddle, J. W., Williams, P., McGowan, J. E. Jr., Tenover, F. C.
(2004). Utility of NCCLS Guidelines for Identifying Extended-Spectrum {beta}-Lactamases in Non-Escherichia coli and Non-Klebsiella spp. of Enterobacteriaceae. J. Clin. Microbiol.
42: 294-298
[Abstract] [Full Text] -
Edelstein, M., Pimkin, M., Palagin, I., Edelstein, I., Stratchounski, L.
(2003). Prevalence and Molecular Epidemiology of CTX-M Extended-Spectrum {beta}-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae in Russian Hospitals. Antimicrob. Agents Chemother.
47: 3724-3732
[Abstract] [Full Text] -
Bell, J. M., Turnidge, J. D., Jones, R. N., the SENTRY Asia-Pacific Participants,,
(2003). Prevalence of Extended-Spectrum {beta}-Lactamase-Producing Enterobacter cloacae in the Asia-Pacific Region: Results from the SENTRY Antimicrobial Surveillance Program, 1998 to 2001. Antimicrob. Agents Chemother.
47: 3989-3993
[Abstract] [Full Text] -
Nagano, N., Shibata, N., Saitou, Y., Nagano, Y., Arakawa, Y.
(2003). Nosocomial Outbreak of Infections by Proteus mirabilis That Produces Extended-Spectrum CTX-M-2 Type {beta}-Lactamase. J. Clin. Microbiol.
41: 5530-5536
[Abstract] [Full Text] -
Arpin, C., Dubois, V., Coulange, L., Andre, C., Fischer, I., Noury, P., Grobost, F., Brochet, J.-P., Jullin, J., Dutilh, B., Larribet, G., Lagrange, I., Quentin, C.
(2003). Extended-Spectrum {beta}-Lactamase-Producing Enterobacteriaceae in Community and Private Health Care Centers. Antimicrob. Agents Chemother.
47: 3506-3514
[Abstract] [Full Text] -
Paterson, D. L., Hujer, K. M., Hujer, A. M., Yeiser, B., Bonomo, M. D., Rice, L. B., Bonomo, R. A., the International Klebsiella Study Group,,
(2003). Extended-Spectrum {beta}-Lactamases in Klebsiella pneumoniae Bloodstream Isolates from Seven Countries: Dominance and Widespread Prevalence of SHV- and CTX-M-Type {beta}-Lactamases. Antimicrob. Agents Chemother.
47: 3554-3560
[Abstract] [Full Text] -
Aumeran, C., Chanal, C., Labia, R., Sirot, D., Sirot, J., Bonnet, R.
(2003). Effects of Ser130Gly and Asp240Lys Substitutions in Extended-Spectrum {beta}-Lactamase CTX-M-9. Antimicrob. Agents Chemother.
47: 2958-2961
[Abstract] [Full Text] -
Bonnet, R., Recule, C., Baraduc, R., Chanal, C., Sirot, D., De Champs, C., Sirot, J.
(2003). Effect of D240G substitution in a novel ESBL CTX-M-27. J Antimicrob Chemother
52: 29-35
[Abstract] [Full Text] -
Dhawan, B., Bonnet, R., Shukla, N. K., Mathur, P., Das, B. K., Kapil, A.
(2003). Infection with an Extended-Spectrum {beta}-Lactamase-Producing Strain of Serratia marcescens following Tongue Reconstruction. J. Clin. Microbiol.
41: 2233-2234
[Abstract] [Full Text] -
Neuwirth, C., Siebor, E., Pruneaux, M., Zarnayova, M., Simonin, C., Kisterman, J. P., Labia, R.
(2003). First isolation of CTX-M15-producing Escherichia coli from two French patients. J Antimicrob Chemother
51: 471-473
[Full Text] -
Poirel, L., Kampfer, P., Nordmann, P.
(2002). Chromosome-Encoded Ambler Class A {beta}-Lactamase of Kluyvera georgiana, a Probable Progenitor of a Subgroup of CTX-M Extended-Spectrum {beta}-Lactamases. Antimicrob. Agents Chemother.
46: 4038-4040
[Abstract] [Full Text] -
Poirel, L., Gniadkowski, M., Nordmann, P.
(2002). Biochemical analysis of the ceftazidime-hydrolysing extended-spectrum {beta}-lactamase CTX-M-15 and of its structurally related {beta}-lactamase CTX-M-3. J Antimicrob Chemother
50: 1031-1034
[Abstract] [Full Text] -
Bou, G., Cartelle, M., Tomas, M., Canle, D., Molina, F., Moure, R., Eiros, J. M., Guerrero, A.
(2002). Identification and Broad Dissemination of the CTX-M-14 {beta}-Lactamase in Different Escherichia coli Strains in the Northwest Area of Spain. J. Clin. Microbiol.
40: 4030-4036
[Abstract] [Full Text] -
Bonnet, R., Chanal, C., Ageron, E., Sirot, D., De Champs, C., Grimont, P., Sirot, J.
(2002). Inducible AmpC {beta}-Lactamase of a New Member Enterobacteriaceae. Antimicrob. Agents Chemother.
46: 3316-3319
[Abstract] [Full Text] -
Baraniak, A., Fiett, J., Hryniewicz, W., Nordmann, P., Gniadkowski, M.
(2002). Ceftazidime-hydrolysing CTX-M-15 extended-spectrum {beta}-lactamase (ESBL) in Poland. J Antimicrob Chemother
50: 393-396
[Abstract] [Full Text] -
Arduino, S. M., Roy, P. H., Jacoby, G. A., Orman, B. E., Pineiro, S. A., Centron, D.
(2002). blaCTX-M-2 Is Located in an Unusual Class 1 Integron (In35) Which Includes Orf513. Antimicrob. Agents Chemother.
46: 2303-2306
[Abstract] [Full Text] -
Cao, V., Lambert, T., Courvalin, P.
(2002). ColE1-Like Plasmid pIP843 of Klebsiella pneumoniae Encoding Extended-Spectrum {beta}-Lactamase CTX-M-17. Antimicrob. Agents Chemother.
46: 1212-1217
[Abstract] [Full Text] -
Petroni, A., Corso, A., Melano, R., Cacace, M. L., Bru, A. M., Rossi, A., Galas, M.
(2002). Plasmidic Extended-Spectrum {beta}-Lactamases in Vibrio cholerae O1 El Tor Isolates in Argentina. Antimicrob. Agents Chemother.
46: 1462-1468
[Abstract] [Full Text] -
Coque, T. M., Oliver, A., Perez-Diaz, J. C., Baquero, F., Canton, R.
(2002). Genes Encoding TEM-4, SHV-2, and CTX-M-10 Extended-Spectrum {beta}-Lactamases Are Carried by Multiple Klebsiella pneumoniae Clones in a Single Hospital (Madrid, 1989 to 2000). Antimicrob. Agents Chemother.
46: 500-510
[Abstract] [Full Text] -
Radice, M., Power, P., Di Conza, J., Gutkind, G., Bonnet, R., Sirot, D., Sirot, J., Labia, R.
(2002). Early Dissemination of CTX-M-Derived Enzymes in South America. Antimicrob. Agents Chemother.
46: 602-604
[Full Text]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Copyright © 2009 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»