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Antimicrobial Agents and Chemotherapy, March 2001, p. 878-882, Vol. 45, No. 3
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.3.878-882.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Molecular and Biochemical Analysis of AST-1, a Class A
-Lactamase from Nocardia asteroides Sensu
Stricto
Laurent
Poirel,1
Frederic
Laurent,1,2,3
Thierry
Naas,1
Roger
Labia,4
Patrick
Boiron,3 and
Patrice
Nordmann1,*
Service de Bactériologie-Virologie, Hôpital de
Bicêtre, Assistance Publique/Hôpitaux de Paris,
Faculté de Médecine Paris-Sud, 94275 Le
Kremlin-Bicêtre Cedex,1 Service de
Bactériologie, Hôpital Lyon-Sud, Hospices Civils de Lyon,
Faculté de Médecine Lyon-Sud, 69921 Oullins
Cedex,2 Laboratoire de mycologie
fondamentale et appliquée aux biotechnologies industrielles,
Institut des Sciences Pharmaceutiques et Biologiques, 69373 Lyon Cedex
08,3 and UMR175 CNRS Chimie et
Biologie des Substances Actives, 29000 Quimper,4
France
Received 22 June 2000/Returned for modification 1 October
2000/Accepted 15 December 2000
 |
ABSTRACT |
A 
-lactamase gene was cloned from a Nocardia
asteroides sensu stricto clinical isolate. A recombinant plasmid,
pAST-1, expressed the -lactamase AST-1 in Escherichia
coli JM109. Its pI was 4.8, and its relative molecular mass was
31 kDa. E. coli JM109(pAST-1) was resistant to penicillins
and narrow-spectrum cephalosporins. The -lactamase AST-1 had a
restricted hydrolytic activity spectrum. Its activity was
partially inhibited by clavulanic acid but not by sulbactam and
tazobactam. AST-1 is an Ambler class A -lactamase sharing 65% amino
acid identity with -lactamase FAR-1, the most closely related enzyme.
| |
INTRODUCTION |
The Nocardia genus
includes several species that are opportunistic pathogens in
immunocompromised patients (3, 13). Species of
Nocardia asteroides sensu stricto are the predominant human pathogens and are involved in pulmonary and brain abscesses
(13). Since nocardiosis requires a long treatment (6 to 12 months or longer) and may cause a high mortality rate, the choice of
the optimal antibiotic treatement is crucial (7).
-Lactams have been used as first-line treatment with little concern
for the -lactam susceptibility of Nocardia sp. isolates (13). Knowledge of the mechanisms of -lactam resistance
profiles of Nocardia isolates may be critical for assessing
the potential clinical efficacy of -lactams. A study of the
antimicrobial susceptibility patterns of 78 clinical isolates belonging
to the N. asteroides complex found that 95% of the isolates
exhibit one of the four major antibiotic resistance patterns
(24). Type I (20% of the isolates) is susceptible to
ampicillin and carbenicillin but intermediate in susceptibility to
imipenem; type III (18%) is susceptible to ampicillin and
erythromycin; type V (17%) is resistant to broad-spectrum cephalosporins; and type VI, the most prevalent group (35%), is resistant to ampicillin but susceptible to extended-spectrum
cephalosporins and imipenem. Type II and type IV are extremely
rare and not well characterized. Wallace et al. show that drug
resistance patterns of type III and type V correlate with taxonomic
groups and have been reclassified as Nocardia nova and
Nocardia farcinica, respectively (21,
22). Isolates belonging to types I, IV, and VI are grouped into
the same subspecies, named N. asteroides sensu stricto.
Although some nocardial -lactamases have been characterized
biochemically in N. asteroides (9, 17),
Nocardia brasiliensis (19, 23), and N. farcinica (11, 20), the accurate role of
-lactamase in the -lactam resistance pattern has scarcely been
explored. Sequences of -lactamase genes are available only for
N. farcinica and the nonhuman pathogen Nocardia
lactamdurans (5, 11).
We report on the molecular and biochemical characterization of a class
A -lactamase named AST-1 from a clinical isolate belonging to the
most prevalent group of N. asteroides sensu stricto species. Hydrolytic activity of -lactamase AST-1 was compared to that of
-lactamase FAR-1.
| |
MATERIALS AND METHODS |
Bacterial strains and plasmids.
The N. asteroides
sensu stricto isolate JPL was from a pulmonary abscess of a 30-year-old
human immunodeficiency virus-infected man. It was identified by
molecular methods based on the restriction analysis of PCR fragments
corresponding to the heat shock protein gene, as described previously
(12, 18). The recipient strain Escherichia coli
JM109 for cloning experiments and phagemid cloning vector pBK-CMV have
been reported previously (11).
Antimicrobial agents and MIC determinations.
Antibiotic
powders and their sources have been described previously
(11). Antibiogram disks were used for routine
antibiograms (Sanofi-Diagnostics Pasteur, Marnes-La-Coquette,
France). MICs were determined by an agar dilution technique on
Mueller-Hinton agar (Sanofi-Diagnostics Pasteur) with an inoculum of
104 CFU per spot as reported previously (11).
All plates were incubated at 35°C for 18 h for E. coli and for 72 h for N. asteroides according to
NCCLS guidelines (15). MICs of -lactams were determined alone or in combination with a fixed concentration of clavulanic acid
(2 µg/ml), sulbactam (8 µg/ml), and tazobactam (4 µg/ml).
Cloning experiments and genetic analysis.
Genomic DNA from
N. asteroides sensu stricto JPL was extracted as previously
described (13). Partially digested Sau3AI
fragments of genomic DNA of N. asteroides JPL were ligated
into BamHI-restricted phagemid pBK-CMV (Stratagene, La
Jolla, Calif.). Ligation was performed at a 1:2 vector/insert ratio at
a final concentration of 200 ng of DNA in a ligation mixture containing
1 U of T4 DNA ligase at 4°C for 18 h. Recombinant plasmids were
transformed by electroporation (Gene Pulser II; Bio-Rad,
Ivry-sur-Seine, France) into electrocompetent E. coli JM109
cells. Antibiotic-resistant colonies were selected onto Trypticase soy
(TS) agar plates containing amoxicillin (50 µg/ml) and kanamycin (30 µg/ml) that were analyzed as described previously (13).
Plasmid DNAs of recombinant strains were obtained using Qiagen columns
(Qiagen, Courtaboeuf, France). Plasmid mapping was performed after
double restriction analysis. DNA of one recombinant plasmid with the
shortest insert was sequenced on both strands by using an ABI 377 sequencer (Applied Biosystems, Foster City, Calif.). The nucleotide and
the deduced protein sequences were analyzed with software
available over the internet at the National Center of Biotechnology
Information webwite (http://www.ncbi.nlm.nih.gov) and at
Pedro's Biomolecular Research Tools website
(http://www.fmi.chbiology/research_tools.html).
-Lactamase preparation.
Cultures of E. coli
JM109 harboring recombinant plasmid pAST-1 were grown overnight at
37°C in 4 liters of TS broth with amoxicillin (50 µg/ml). The
bacteria were harvested for 10 min at 6,000 × g, and
the bacterial pellet was resuspended in 30 ml of 20 mM bis-Tris (pH
5.5) [bis(2-hydroxyethylimino)tris(hydroxymethyl)methane] at
4°C. The bacterial cells were disrupted by sonication (two times for
20 s at 20 Hz) (Vibra Cell 75022 Phospholyser; Bioblock, Illkirch,
France) and were centrifuged (30 min, 10,000 × g,
4°C). The supernatant containing the enzyme extract was purified by ion-exchange chromatography with AGMP-1 exchanger (Bio-Rad). The exchanger in the chloride form was treated with 0.1 M ammonia in water
and was then washed extensively with water. After adsorption of the
extracts, elution was performed with 0.1 M NaCl. The active fractions
were pooled, dialyzed extensively, and lyophilized.
Kinetic measurements.
Kinetic measurements were performed
with the semipurified -lactamase preparation extracted from E. coli JM109(pAST-1). The kinetic constants were determined by the
online computerized microacidimetric method at pH 7.0 and 37°C as
described previously (10). Vmax and
Vmax/Km were expressed
relative to that of benzylpenicillin (Vmax = 100). The 50% inhibitory concentrations (IC50s) were
determined for clavulanate, sulbactam, and tazobactam as the
concentration that reduced the hydrolysis rate of 100 µM
benzylpenicillin by 50% under conditions in which the enzyme was
preincubated with various concentrations of inhibitor for 5 min at
30°C before addition of the benzylpenicillin (10). The
specific activity of the semipurified enzyme from E. coli
JM109 harboring pAST-1 (AST-1) was obtained as described previously
(16). One unit of the enzyme was defined as the activity
which hydrolyzed 100 µmol of cephalothin per min per mg of protein.
The total protein content was determined with bovin serum albumin as
the standard (Bio-Rad DC protein assay kit).
IEF and determination of relative molecular mass.
Cultures
of N. asteroides JPL were grown in TS broth at 35°C for 72 h in an aerobic atmosphere. -Lactamase extracts from these cultures
were obtained as described previously (11) and were
submitted with the -lactamase preparation from cultures of E. coli JM109 harboring recombinant plasmid pAST-1 to isoelectric focusing (IEF) analysis on an ampholine polyacrylamide gel, as described previously (11). The relative molecular mass of
the -lactamase from E. coli JM109(pAST-1) culture was
estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis
analysis, as reported previously (16).
Nucleotide sequence accession number.
The nucleotide
sequence data reported in this paper have been assigned to the GenBank
nucleotide database under accession no. AF 279904.
| |
RESULTS AND DISCUSSION |
Identification and susceptibility testing of N. asteroides sensu stricto isolate.
The N. asteroides isolate JPL was assigned to the type VI group of
Steingrube et al. (18), which includes most of the
N. asteroides sensu stricto isolates. MICs of -lactams
showed that this isolate was resistant to amino- and
ureidopenicillins, narrow-spectrum cephalosporins, ceftazidime, and
aztreonam (Table 1). Addition of
clavulanate partially decreased the MICs of amino- and
ureidopenicillins, while tazobactam and sulbactam did not have any
significant effect (Table 1). These results were consistent with those
obtained for other N. asteroides isolates (9),
for N. farcinica (11, 20), and for
Mycobacterium fortuitum (2, 6). Disk
susceptibility testing showed that the N. asteroides isolate
JPL was also susceptible to aminoglycosides (except kanamycin),
tetracycline, and sulfonamides and resistant to fluoroquinolones,
macrolides, fosfomycin, and chloramphenicol.
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TABLE 1.
MICs of -lactams for N. asteroides sensu
stricto JPL, E. coli JM109 harboring recombinant
plasmid pAST-1, and reference strain E. coli JM109
|
|
Characterization of the blaAST-1 gene and
its expression in E. coli.
Two recombinant plasmids
were obtained harboring the same 1.7-kb insert as a result of cloning
experiments. One of them, pAST-1, was further characterized, and its
insert was sequenced. It contained a 933-bp open reading frame (ORF),
blaAST-1, encoding a 310-amino-acid protein named AST-1 (Fig. 1). The G+C
content of blaAST-1 was 71.3%, which lies
within the G+C ratios for other chromosomally encoded
Nocardia sp. genes as recorded in the EMBL and GenBank sequence databases (64 to 72%). Moreover, 18 bp upstream of this ORF,
part of another ORF was identified, the deduced protein of which shared
42% identity with a 561-amino-acid protein of unknown function
from Streptomyces coelicolor (GenBank accession no. T35845). Additionally, 244 bp from blaAST-1,
another ORF was identified, the protein of which shared 59%
amino acid identity (within 89 amino acids) with a probable
phosphorylating protein, UreD, from Mycobacterium leprae
(GenBank accession no. S72992). These results are consistent with the
Actinomycetales origin of blaAST-1. Since no ATG initiation codon was found for
blaAST-1, a putative GTG was retained as its
initiation codon (data not shown), as in several
Streptomyces and Mycobacterium sp. genes
(11). Within the deduced protein, structural elements
characteristic of serine and Ambler class A -lactamases
were identified (1, 8) (Fig. 1). The comparison of the
AST-1 sequence with those of other class A -lactamases showed that
it was distantly related to class A -lactamases, including those of
Streptomyces and Mycobacterium spp. (35 to 50%
of amino acid identity). It was related mostly to FAR-1 -lactamase
from N. farcinica VIC, sharing 65% amino acid identity
(11).
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FIG. 1.
Alignment of the amino acid sequence of AST-1 with those
of TEM-1 and FAR-1 -lactamases. Numbering is performed according to
the method described by Ambler et al. (1). The conserved
residues among nocardial -lactamases are reported below the
alignment, with dots indicating conserved residues. Four structural
elements characteristic of class A -lactamases are boxed in grey.
Some relevant amino acid positions that may correspond to amino acid
changes in extended-spectrum TEM derivatives are indicated by
asterisks. Dashes indicate gaps within the alignment.
|
|
MICs of
-lactams for
E. coli JM109(pAST-1) showed
mostly resistance to penicillins that was partially antagonized by
addition
of clavulanate (Table
1). These MICs mirrored those obtained
for
N. asteroides isolate JPL and for
E. coli
JM109(pFAR-1) expressing
-lactamase FAR-1, except that in this
latter case, a slight increase
of the MIC of aztreonam was observed
(
11).
Biochemical properties of the -lactamase AST-1.
IEF
analysis showed that cultures of N. asteroides isolate JPL
and of E. coli JM109(pAST-1) produced an identical
-lactamase with a pI of 4.8 (data not shown). This pI was similar to
those observed for -lactamases of other N. asteroides
isolates (4.2 to 4.6) (9) and was different from the pI of
5.8 of an N. asteroides isolate, as reported recently
(17). Thus, N. asteroides isolates may possess
different -lactamases of acidic pI values. However, valid comparison
of -lactamase content based on pI values is difficult, since in
the previous studies (9, 17), N. asteroides sensu stricto isolates were not differentiated from other
N. asteroides spp. by molecular techniques.
The relative molecular mass of the
-lactamase AST-1 expressed in
E. coli JM109(pAST-1) was estimated to be 31 kDa (data
not
shown), close to the value of 32 kDa for the
-lactamase FAR-1
(
11).
The
-lactamase AST-1 was very poorly expressed from
E. coli JM109(pAST-1) and
N. asteroides
JPL cultures (data not shown).
The specific activity of the
semipurified extract of
E. coli JM109(pAST-1)
was 0.11 mU · mg of protein
1 with 100 µM cephalothin as the
substrate. Its purification factor
was between 10- and 15-fold. Kinetic
parameters of
-lactamase
AST-1 revealed its strong activity against
penicillins and narrow-spectrum
cephalosporins (Table
2). As opposed to
-lactamase FAR-1,
hydrolysis
of aztreonam was not detected. As assessed by
IC
50s, the activity
of inhibitors was weak, especially for
sulbactam and tazobactam
(Table
3).
Similar results were obtained for
-lactamases extracted
from
N. asteroides,
M. fortuitum, and
N. farcinica (FAR-1) isolates
(
2,
6,
9,
11). Thus, it
may be hypothesized that
-lactamases
of
Nocardia spp. are
not susceptible to the
-lactamase inhibitors
sulbactam and
tazobactam. Susceptibility of
N. brasiliensis -lactamases
to clavulanate is, however, greater than that of AST-1
(
22).
In one report, hydrolytic activity toward
cefotaxime was noted
for
N. asteroides isolates
(
17). However, comparison with the
activity of AST-1
is difficult, again since these
N. asteroides isolates have
not been grouped by molecular techniques (
17).
AST-1, like FAR-1, is tazobactam resistant, like the
inhibitor-resistant TEM derivatives occurring as acquired resistance
mechanisms. Thus, AST-1 is another example of naturally occurring
inhibitor-resistant
-lactamases that mimic molecular mechanisms
involved in acquired
-lactam resistance. It would be interesting
to
investigate whether the
N. asteroides isolate JPL
produces
clavulanate derivatives in a manner similar to that of
the
-lactamase-producing
N. lactamdurans isolate, which
produces cephamycin derivatives
(
5). Since AST-1
activity is partially or totally resistant
to inhibitors,
antibiotic combinations containing amoxicillin-clavulanate,
piperacillin-tazobactam, and ampicillin-sulbactam should be avoided
in
treatment of nocardiosis due to
N. asteroides sensu
stricto.
AST-1, as opposed to
-lactamase FAR-1, did not hydrolyze
aztreonam. A few substitutions in TEM-derivative
-lactamases, such
as Glu104Lys, Gly238Ser, and Glu240Lys,
increase hydrolytic activity
toward aztreonam (
4,
14).
FAR-1 possessed a serine residue
in positions 104 and 240, as not found
in the AST-1 sequence (Fig.
1). Thus, sequence differences between the
two nocardial
-lactamases
may account for the observed difference in
the hydrolytic activity
toward the monobactam aztreonam. Moreover,
proline in position
238 in AST-1 sequence may modify the
-3 sheet
structure, thus
explaining the weak catalytic properties of AST-1.
Conclusion.
-Lactamase AST-1 is the second class A
-lactamase characterized in a Nocardia sp. clinical
isolate. As already mentioned for -lactamase FAR-1 from
N. farcinica, AST-1 expression cannot explain the entire
-lactam resistance profile of the N. asteroides sensu
stricto isolate, especially concerning its resistance to aztreonam and
ceftazidime. Additionally, other undetected -lactamases and/or
penicillin-binding affinities may account for this naturally occurring
-lactam resistance profile. Since AST-1 and FAR-1
-lactamases shared significant amino acid identity and similar
biochemical properties, they may derive from a common ancestor.
| |
ACKNOWLEDGMENTS |
L.P. and F.L. contributed equally to this work.
This work was funded by a grant from the Ministères de
l'Education Nationale et de la Recherche (UPRES-JE 2227),
Université Paris XI, Faculté de Médecine Paris-Sud, France.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Service de
Bactériologie-Virologie, Hôpital de Bicêtre, 78 rue
du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex,
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.
| |
REFERENCES |
| 1.
|
Ambler, R. P.,
A. F. W. Coulson,
J.-M. Frère,
J. M. Guysen,
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.
|
Amicosante, G.,
N. Franceschini,
B. Segatore,
A. Oratore,
L. Fattorini,
G. Orefici,
J. Van Beeumen, and J.-M. Frère.
1990.
Characterization of a beta-lactamase produced in Mycobacterium fortuitum D316.
Biochem. J.
271:729-734[Medline].
|
| 3.
|
Beaman, B. L.,
P. Boiron,
L. Beaman,
G. H. Brownell,
K. Schaal, and M. E. Gombert.
1992.
Nocardia and nocardiosis.
J. Med. Vet. Mycol.
30:317-331.
|
| 4.
|
Cantu, C., III,
W. Huang, and T. Palzkill.
1996.
Selection and characterization of amino acid substitutions at residues 237-240 of TEM-1 beta-lactamase with altered substrate specificity for aztreonam and ceftazidime.
J. Biol. Chem.
271:22538-22545[Abstract/Free Full Text].
|
| 5.
|
Coque, J. J.,
P. Liras, and J. F. Martin.
1993.
Genes for a -lactamase, a penicillin-binding protein and a transmembrane protein are clustered with the cephamycin biosynthetic genes in Nocardia lactamdurans.
EMBO J.
12:631-639[Medline].
|
| 6.
|
Fattorini, L.,
G. Amicosante,
D. Fiorentino,
N. Franceschini,
L. Di Marzio,
A. Oratore, and G. Orefici.
1989.
Inhibitors and inactivators of beta-lactamase from Mycobacterium fortuitum.
J. Chemother.
1:293-297[Medline].
|
| 7.
|
Gombert, M. E.,
L. B. Berkowitz,
T. M. Aulicino, and L. Dubouchet.
1990.
Therapy of pulmonary nocardiosis in immunocompromised mice.
Antimicrob. Agents Chemother.
34:1766-1768[Abstract/Free Full Text].
|
| 8.
|
Joris, B.,
P. Ledent,
O. Dideberg,
E. Fonze,
J. Lamotte-Brasseur,
J. A. Kelly,
J.-M. Ghuysen, and J.-M. Frère.
1991.
Comparison of the sequences of class A -lactamases and of the secondary structure elements of penicillin-recognizing proteins.
Antimicrob. Agents Chemother.
35:2294-2301[Abstract/Free Full Text].
|
| 9.
|
Kitzis, M. D.,
L. Gutmann, and J. F. Acar.
1985.
In-vitro susceptibility of Nocardia asteroides to 21 beta-lactam antibiotics, in combination with three beta-lactamase inhibitors, and its relationship to the beta-lactamase content.
J. Antimicrob. Chemother.
15:23-30[Abstract/Free Full Text].
|
| 10.
|
Labia, R.,
J. Andrillon, and F. Legoffic.
1973.
Computerized microacidimetric determination of -lactamase Michaelis-Menten constants.
FEBS Lett.
33:42-44[CrossRef][Medline].
|
| 11.
|
Laurent, F.,
L. Poirel,
T. Naas,
E. B. Chaibi,
R. Labia,
P. Boiron, and P. Nordmann.
1999.
Biochemical-genetic analysis and distribution of FAR-1, a class A -lactamase from Nocardia farcinica.
Antimicrob. Agents Chemother.
43:1644-1650[Abstract/Free Full Text].
|
| 12.
|
Laurent, F. J.,
F. Provost, and P. Boiron.
1998.
Rapid identification of clinically relevant Nocardia species to genus level by 16S rRNA gene PCR.
J. Clin. Microbiol.
37:99-102[Abstract/Free Full Text].
|
| 13.
|
Lerner, P. I.
1996.
Nocardiosis.
Clin. Infect. Dis.
22:891-903[Medline].
|
| 14.
|
Matagne, A.,
J. Lamotte-Brasseur, and J.-M. Frère.
1998.
Catalytic properties of class A beta-lactamases: efficiency and diversity.
Biochem. J.
330:581-598.
|
| 15.
|
National Committee for Clinical Laboratory Standards.
1993.
Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A3.
National Committee for Clinical Laboratory Standards, Villanova, Pa.
|
| 16.
|
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[Abstract/Free Full Text].
|
| 17.
|
Scopetti, F.,
L. Fattorini,
N. Franceschini,
G. Amicosante, and G. Orefici.
1997.
Non-inducible, mainly cell-associated -lactamase from Nocardia asteroides strain 108.
J. Antimicrob. Chemother.
40:5-11[Abstract/Free Full Text].
|
| 18.
|
Steingrube, V. A.,
B. A. Brown,
J. L. Gibson,
R. W. Wilson,
J. Brown,
Z. Blacklock,
K. Jost,
S. Locke,
R. F. Ulrich, and R. J. Wallace, Jr.
1995.
DNA amplification and restriction endonuclease analysis for differentiation of 12 species and taxa of Nocardia, including recognition of four new taxa within the Nocardia asteroides complex.
J. Clin. Microbiol.
33:3096-3101[Abstract].
|
| 19.
|
Steingrube, V. A.,
R. J. Wallace, Jr.,
B. A. Brown,
Y. Pang,
B. Zeluff,
L. C. Steele, and Y. Zhang.
1991.
Acquired resistance of Nocardia brasiliensis to clavulanic acid related to a change in -lactamase following therapy with amoxicillin-clavulanic acid.
Antimicrob. Agents Chemother.
35:524-528[Abstract/Free Full Text].
|
| 20.
|
Steingrube, V. A.,
R. J. Wallace, Jr.,
B. A. Brown,
Y. Zhang,
L. C. Steele,
G. Young, and D. R. Nash.
1993.
Partial characterization of Nocardia farcinica -lactamases.
Antimicrob. Agents Chemother.
37:1850-1855[Abstract/Free Full Text].
|
| 21.
|
Wallace, R. J., Jr.,
B. A. Brown,
M. Tsukamura,
J. M. Brown, and G. O. Onyi.
1991.
Clinical and laboratory features of Nocardia nova.
J. Clin. Microbiol.
29:2407-2411[Abstract/Free Full Text].
|
| 22.
|
Wallace, R. J., Jr.,
D. R. Nash,
W. K. Johnson,
L. C. Steele, and V. A. Steingrube.
1987.
Beta-lactam resistance in Nocardia brasiliensis is mediated by beta-lactamase and reversed in the presence of clavulanic acid.
J. Infect. Dis.
156:959-966[Medline].
|
| 23.
|
Wallace, R. J., Jr.,
L. C. Steele,
G. Sumter, and J. M. Smith.
1988.
Antimicrobial susceptibility patterns of Nocardia asteroides.
Antimicrob. Agents Chemother.
32:1776-1779[Abstract/Free Full Text].
|
| 24.
|
Wallace, R. J., Jr.,
M. Tsukamura,
B. A. Brown,
J. Brown,
V. A. Steingrube,
Y. S. Zhang, and D. R. Nash.
1990.
Cefotaxime-resistant Nocardia asteroides strains are isolates of the controversial species Nocardia farcinica.
J. Clin. Microbiol.
28:2726-2732[Abstract/Free Full Text].
|
Antimicrobial Agents and Chemotherapy, March 2001, p. 878-882, Vol. 45, No. 3
0066-4804/01/$04.00+0 DOI: 10.1128/AAC.45.3.878-882.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
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-
Sauvage, E., Fonze, E., Quinting, B., Galleni, M., Frere, J.-M., Charlier, P.
(2006). Crystal Structure of the Mycobacterium fortuitum Class A {beta}-Lactamase: Structural Basis for Broad Substrate Specificity.. Antimicrob. Agents Chemother.
50: 2516-2521
[Abstract]
[Full Text]
-
Jacoby, G. A.
(2006). {beta}-Lactamase Nomenclature.. Antimicrob. Agents Chemother.
50: 1123-1129
[Full Text]
-
McDonough, J. A., Hacker, K. E., Flores, A. R., Pavelka, M. S. Jr, Braunstein, M.
(2005). The Twin-Arginine Translocation Pathway of Mycobacterium smegmatis Is Functional and Required for the Export of Mycobacterial {beta}-Lactamases. J. Bacteriol.
187: 7667-7679
[Abstract]
[Full Text]
-
Lartigue, M.-F., Poirel, L., Fortineau, N., Nordmann, P.
(2005). Chromosome-Borne Class A BOR-1 {beta}-Lactamase of Bordetella bronchiseptica and Bordetella parapertussis. Antimicrob. Agents Chemother.
49: 2565-2567
[Abstract]
[Full Text]
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Abstract
Introduction
