Browse
Submit Data
Databases
API
Help

Dataset Information

29 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

BEL-2, an extended-spectrum beta-lactamase with increased activity toward expanded-spectrum cephalosporins in Pseudomonas aeruginosa.

ABSTRACT: A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ss-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The bla(BEL-2) gene was identified from a P. aeruginosa isolate clonally related to another bla(BEL-1)-positive isolate.

SUBMITTER: Poirel L

PROVIDER: S-EPMC2798549 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

BEL-2, an extended-spectrum beta-lactamase with increased activity toward expanded-spectrum cephalosporins in Pseudomonas aeruginosa.

Poirel Laurent L Docquier Jean-Denis JD De Luca Filomena F Verlinde Annemie A Ide Louis L Rossolini Gian Maria GM Nordmann Patrice P

Antimicrobial agents and chemotherapy 20091102 1

A Pseudomonas aeruginosa isolate recovered in Belgium produced a novel extended-spectrum ss-lactamase, BEL-2, differing from BEL-1 by a single Leu162Phe substitution. That modification significantly altered the kinetic properties of the enzyme, increasing its affinity for expanded-spectrum cephalosporins. The bla(BEL-2) gene was identified from a P. aeruginosa isolate clonally related to another bla(BEL-1)-positive isolate. ...[more]

PMID: 19884378

Similar Datasets

OXA-163, an OXA-48-related class D ?-lactamase with extended activity toward expanded-spectrum cephalosporins.

Project description:Two bla(OXA-48)-like-positive isolates (Klebsiella pneumoniae and Enterobacter cloacae) were recovered in Argentina in 2008 as part of a large-scale survey focused on multidrug resistance in Enterobacteriaceae. In both cases, sequencing identified ?-lactamase OXA-163, differing from OXA-48 by a single amino substitution and a 4-amino-acid deletion. OXA-163 hydrolyzed penicillins, ceftazidime, and cefotaxime, whereas OXA-48 did not. However, OXA-163 had a much lower ability to hydrolyze carbapenems than OXA-48, therefore barely being considered a carbapenemase. In both isolates, the bla(OXA-163) gene was located on plasmids that differed in structure and size. However, a detailed genetic analysis revealed a similar genetic context in those isolates, with the bla(OXA-163) gene being bracketed by novel transposase genes, making this genetic environment different from that reported for the bla(OXA-48) gene. This study identified the first class D ?-lactamase compromising both extended-spectrum cephalosporin and carbapenem activities.

| S-EPMC3101449 | biostudies-literature

Integron-encoded GES-type extended-spectrum beta-lactamase with increased activity toward aztreonam in Pseudomonas aeruginosa.

Project description:A Pseudomonas aeruginosa strain expresses an extended-spectrum beta-lactamase, GES-9, which differs from GES-1 by a Gly243Ser substitution, is inhibited by clavulanic acid and imipenem, and hydrolyzes aztreonam. The bla(GES-9) gene was located inside a class 1 integron structure containing two copies of a novel insertion sequence belonging to the IS1111 family.

| S-EPMC1196234 | biostudies-literature

Crystal Structure of the Pseudomonas aeruginosa BEL-1 Extended-Spectrum ?-Lactamase and Its Complexes with Moxalactam and Imipenem.

Project description:BEL-1 is an acquired class A extended-spectrum ?-lactamase (ESBL) found in Pseudomonas aeruginosa clinical isolates from Belgium which is divergent from other ESBLs (maximum identity of 54% with GES-type enzymes). This enzyme is efficiently inhibited by clavulanate, imipenem, and moxalactam. Crystals of BEL-1 were obtained at pH 5.6, and the structure of native BEL-1 was determined from orthorhombic and monoclinic crystal forms at 1.60-Å and 1.48-Å resolution, respectively. By soaking native BEL-1 crystals, complexes with imipenem (monoclinic form, 1.79-Å resolution) and moxalactam (orthorhombic form, 1.85-Å resolution) were also obtained. In the acyl-enzyme complexes, imipenem and moxalactam differ by the position of the ?-substituent and of the carbonyl oxygen (in or out of the oxyanion hole). More surprisingly, the ?-loop, which includes the catalytically relevant residue Glu166, was found in different conformations in the various subunits, resulting in the Glu166 side chain being rotated out of the active site or even in displacement of its C? atom up to approximately 10 Å. A BEL-1 variant showing the single Leu162Phe substitution (BEL-2) confers a higher level of resistance to CAZ, CTX, and FEP and shows significantly lower Km values than BEL-1, especially with oxyiminocephalosporins. BEL-1 Leu162 is located at the beginning of the ?-loop and is surrounded by Phe72, Leu139, and Leu148 (contact distances, 3.5 to 3.9 Å). This small hydrophobic cavity could not reasonably accommodate the bulkier Phe162 found in BEL-2 without altering neighboring residues or the ?-loop itself, thus likely causing an important alteration of the enzyme kinetic properties.

| S-EPMC5118998 | biostudies-literature

BEL-1, a novel clavulanic acid-inhibited extended-spectrum beta-lactamase, and the class 1 integron In120 in Pseudomonas aeruginosa.

Project description:Screening by a double-disk synergy test identified a Pseudomonas aeruginosa isolate that produced a clavulanic acid-inhibited expanded-spectrum beta-lactamase (ESBL). Cloning and sequencing identified a novel ESBL, BEL-1, weakly related to other Ambler class A ESBLs. beta-Lactamase BEL-1 hydrolyzed significantly most expanded-spectrum cephalosporins and aztreonam, and its activity was inhibited by clavulanic acid, tazobactam, cefoxitin, moxalactam, and imipenem. This chromosome-encoded ESBL gene was embedded in a class 1 integron containing three other gene cassettes. In addition, this integron was bracketed by Tn1404 transposon sequences at its right end and by P. aeruginosa-specific sequences at its left end.

| S-EPMC1195426 | biostudies-literature

PME-1, an extended-spectrum ?-lactamase identified in Pseudomonas aeruginosa.

Project description:A novel extended-spectrum ?-lactamase (ESBL) was identified in a Pseudomonas aeruginosa clinical isolate obtained from a patient admitted to a hospital in Pennsylvania in 2008. The patient had a prolonged hospitalization in a hospital in Dubai, United Arab Emirates, before being transferred to the United States. The novel ESBL, designated PME-1 (Pseudomonas aeruginosa ESBL 1), is a molecular class A, Bush-Jacoby-Medeiros group 2be enzyme and shared 50, 43, and 41% amino acid identity with the L2 ?-lactamase of Stenotrophomonas maltophilia, CTX-M-9, and KPC-2, respectively. PME-1 conferred clinically relevant resistance to ceftazidime, cefotaxime, cefepime, and aztreonam in P. aeruginosa PAO1 but not to carbapenems. Purified PME-1 showed good hydrolytic activity against ceftazidime, cefotaxime, and aztreonam, while activity against carbapenems and cefepime could not be measured. PME-1 was inhibited well by ?-lactamase inhibitors, including clavulanic acid, sulbactam, and tazobactam. The bla(PME-1) gene was carried by an approximately 9-kb plasmid and flanked by tandem ISCR24 elements.

| S-EPMC3101390 | biostudies-literature

An SHV-derived extended-spectrum beta-lactamase in Pseudomonas aeruginosa.

Project description:A clinical isolate of Pseudomonas aeruginosa RP-1 produced the extended-spectrum beta-lactamase (ESBL) SHV-2a. Its gene was expressed from a composite promoter made of the -35 region derived from the left inverted repeat of IS26 and the -10 region from the blaSHV-2a promoter itself. The DNA sequences immediately surrounding blaSHV-2a were homologous to plasmid pMPA2a from Klebsiella pneumoniae KpZU-3, while further away and 3' to the blaSHV-2a gene, a sequence corresponding to the left end of Tn1721 was detected, thus indicating a likely enterobacterial origin of this ESBL gene.

| S-EPMC89260 | biostudies-literature

Integrase-Mediated Recombination of the bel-1 Gene Cassette Encoding the Extended-Spectrum β-Lactamase BEL-1.

Project description:Integrons are genetic elements that can acquire and rearrange gene cassettes. The blaBEL-1 gene encodes an extended-spectrum β-lactamase, BEL-1, that is present at the second position of the variable region of class 1 integrons identified in Pseudomonas aeruginosa The mobility of the bel-1 gene cassette was analyzed under physiological conditions and with the integrase gene being overexpressed. Cassette mobility in Escherichia coli was detected by excision/integration into the recipient integron In3 on the conjugative plasmid R388 with the overproduced integrase. Despite several antibiotic pressures, the bel-1 cassette remained at the second position in the integron, highlighting its stability in P. aeruginosa Overexpression of the integrase gene in E. coli induced bel-1 cassette recombination. However, cassettes containing two genes (blaBEL-1 and smr2 or blaBEL-1 and aacA4) were excised, suggesting that the bel-1 cassette attC site was defective. We show that bel-1 is a stable gene cassette under physiological growth conditions, irrespective of the selective antibiotic pressure, that may be mobilized upon overexpression of the integrase gene.

| S-EPMC5923138 | biostudies-literature

IS1999 increases expression of the extended-spectrum beta-lactamase VEB-1 in Pseudomonas aeruginosa.

Project description:The integron-borne bla(VEB-1) gene encodes an extended-spectrum beta-lactamase. This gene was associated mostly with IS1999 and rarely with an additional IS2000 element in Pseudomonas aeruginosa isolates from Thailand, whereas IS1999 was only very rarely associated with bla(VEB-1) in Enterobacteriaceae. Expression experiments and promoter study identified promoter sequences in IS1999 that increased the expression of VEB-1 in P. aeruginosa.

| S-EPMC181007 | biostudies-literature

Extended-spectrum cephalosporinases in Pseudomonas aeruginosa.

Project description:The characterization of AmpC-type beta-lactamases was performed in a collection of 32 clinical Pseudomonas aeruginosa isolates with intermediate susceptibility or resistance to imipenem and ceftazidime. Twenty-one out of those 32 isolates overexpressed AmpC beta-lactamase, and the MICs of ceftazidime and imipenem were reduced after cloxacillin addition. Cloning and sequencing identified 10 AmpC beta-lactamase variants. Reduced susceptibility to imipenem, ceftazidime, and cefepime was observed only with recombinant P. aeruginosa strains expressing an AmpC beta-lactamase that had an alanine residue at position 105. The catalytic efficiencies (k(cat)/K(m)) of the AmpC variants possessing this residue were increased against oxyiminocephalosporins and imipenem. In addition, we show here that those AmpC variants constitute a favorable background for the in vitro selection of imipenem-resistant strains. This report identified a novel resistance mechanism that may contribute to imipenem resistance in P. aeruginosa.

| S-EPMC2681535 | biostudies-literature

OXA-18, a class D clavulanic acid-inhibited extended-spectrum beta-lactamase from Pseudomonas aeruginosa.

Project description:Clinical isolate Pseudomonas aeruginosa Mus showed resistance both to extended-spectrum cephalosporins and to aztreonam. We detected a typical double-disk synergy image when ceftazidime or aztreonam was placed next to a clavulanic acid disk on an agar plate. This resistance phenotype suggested the presence of an extended-spectrum beta-lactamase. Isoelectric focusing revealed that this strain produced three beta-lactamases, of pI 5.5, 7.4, and 8.2. A 2.6-kb Sau3A fragment encoding the extended-spectrum beta-lactamase of pI 5.5 was cloned from P. aeruginosa Mus genomic DNA. This enzyme, named OXA-18, had a relative molecular mass of 30.6 kDa. OXA-18 has a broad substrate profile, hydrolyzing amoxicillin, ticarcillin, cephalothin, ceftazidime, cefotaxime, and aztreonam, but not imipenem or cephamycins. Its activity was totally inhibited by clavulanic acid at 2 microg/ml. Hydrolysis constants of OXA-18 (Vmax, Km) confirmed the MIC results. Cloxacillin and oxacillin hydrolysis was noticeable with the partially purified OXA-18. The blaOXA-18 gene encodes a 275-amino-acid protein which has weak identity with all class D beta-lactamases except OXA-9 and OXA-12 (45 and 42% amino acid identity, respectively). OXA-18 is likely to be chromosomally encoded since no plasmid was found in the strain and because attempts to transfer the resistance marker failed. OXA-18 is peculiar since it is a class D beta-lactamase which confers high resistance to extended-spectrum cephalosporins and seems to have unique hydrolytic properties among non-class A enzymes.

| S-EPMC164091 | biostudies-other

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data