Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

OXA-198, an acquired carbapenem-hydrolyzing class D beta-lactamase from Pseudomonas aeruginosa.

ABSTRACT: A carbapenem-resistant Pseudomonas aeruginosa strain (PA41437) susceptible to expanded-spectrum cephalosporins was recovered from several consecutive lower-respiratory-tract specimens of a patient who developed a ventilator-associated pneumonia while hospitalized in an intensive care unit. Cloning experiments identified OXA-198, a new class D ?-lactamase which was weakly related (less than 45% amino acid identity) to other class D ?-lactamases. Expression in Escherichia coli TOP10 and in P. aeruginosa PAO1 led to transformants that were resistant to ticarcillin and showed reduced susceptibility to carbapenems and cefepime. The bla(OXA-198) gene was harbored by a class 1 integron carried by a ca. 46-kb nontypeable plasmid. This study describes a novel class D ?-lactamase involved in carbapenem resistance in P. aeruginosa.

SUBMITTER: El Garch F

PROVIDER: S-EPMC3186976 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

OXA-198, an acquired carbapenem-hydrolyzing class D beta-lactamase from Pseudomonas aeruginosa.

El Garch Farid F Bogaerts Pierre P Bebrone Carine C Galleni Moreno M Glupczynski Youri Y

Antimicrobial agents and chemotherapy 20110725 10

A carbapenem-resistant Pseudomonas aeruginosa strain (PA41437) susceptible to expanded-spectrum cephalosporins was recovered from several consecutive lower-respiratory-tract specimens of a patient who developed a ventilator-associated pneumonia while hospitalized in an intensive care unit. Cloning experiments identified OXA-198, a new class D β-lactamase which was weakly related (less than 45% amino acid identity) to other class D β-lactamases. Expression in Escherichia coli TOP10 and in P. aeru ...[more]

PMID: 21788473

Similar Datasets

OXA-143, a novel carbapenem-hydrolyzing class D beta-lactamase in Acinetobacter baumannii.

Project description:A carbapenem-resistant Acinetobacter baumannii strain was isolated in Brazil in 2004 in which no known carbapenemase gene was detected by PCR. Cloning experiments, followed by expression in Escherichia coli, gave an E. coli recombinant strain expressing a novel carbapenem-hydrolyzing class D beta-lactamase (CHDL). OXA-143 showed 88% amino acid sequence identity with OXA-40, 63% identity with OXA-23, and 52% identity with OXA-58. It hydrolyzed penicillins, oxacillin, meropenem, and imipenem but not expanded-spectrum cephalosporins. The bla(OXA-143) gene was located on a ca. 30-kb plasmid. After transformation into reference strain A. baumannii ATCC 19606, it conferred resistance to carbapenems. Analysis of the genetic environment of bla(OXA-143) revealed that it was associated with neither insertion sequences nor integron structures. However, it was bracketed by similar replicase-encoding genes at both ends, suggesting acquisition through a homologous recombination process. This study identified a novel class D beta-lactamase involved in carbapenem resistance in A. baumannii. This enzyme is the first member of a novel subgroup of CHDLs whose prevalence remains to be determined.

| S-EPMC2786334 | biostudies-literature

Characterization of OXA-181, a carbapenem-hydrolyzing class D beta-lactamase from Klebsiella pneumoniae.

Project description:Klebsiella pneumoniae KP3 was isolated from a patient transferred from India to the Sultanate of Oman. K. pneumoniae KP3 was resistant to all ?-lactams, including carbapenems, and expressed the carbapenem-hydrolyzing ?-lactamase OXA-181, which differs from OXA-48 by four amino acid substitutions. Compared to OXA-48, OXA-181 possessed a very similar hydrolytic profile. The bla(OXA-181) gene was located on a 7.6-kb ColE-type plasmid and was linked to the insertion sequence ISEcp1. The ISEcp1-mediated one-ended transposition of bla(OXA-181) was also demonstrated.

| S-EPMC3186949 | biostudies-literature

OXA-134, a naturally occurring carbapenem-hydrolyzing class D beta-lactamase from Acinetobacter lwoffii.

Project description:Acinetobacter lwoffii, a species whose natural habitat is the human skin, intrinsically possesses a chromosomal gene encoding a carbapenem-hydrolyzing class D ?-lactamase, OXA-134. This species may therefore constitute a reservoir for carbapenemase genes that may spread among other Acinetobacter species.

| S-EPMC2981293 | biostudies-literature

Characterization of OXA-204, a carbapenem-hydrolyzing class D β-lactamase from Klebsiella pneumoniae.

Project description:A Klebsiella pneumoniae clinical isolate recovered in Tunisia showed resistance to all β-lactams and decreased susceptibility to carbapenems. K. pneumoniae 204 expressed the carbapenem-hydrolyzing β-lactamase OXA-204, differing from OXA-48 by two amino acid substitutions (Gln98His and Thr99Arg) (class D β-lactamase [DBL] numbering). OXA-48 and OXA-204 shared similar resistance profiles, hydrolyzing carbapenems but sparing broad-spectrum cephalosporins. The bla(OXA-204) gene was located on a ca. 150-kb IncA/C-type plasmid, which also carried the bla(CMY-4) gene. The bla(OXA-204) gene was associated with an ISEcp1 element, whereas the bla(OXA-48) genes are usually associated with IS1999.

| S-EPMC3535949 | biostudies-literature

OXA-484, an OXA-48-Type Carbapenem-Hydrolyzing Class D β-Lactamase From <i>Escherichia coli</i>.

Project description:OXA-48-like carbapenemases are among the most frequent carbapenemases in Gram-negative Enterobacterales worldwide with the highest prevalence in the Middle East, North Africa and Europe. Here, we investigated the so far uncharacterized carbapenemase OXA-484 from a clinical E. coli isolate belonging to the high-risk clone ST410 regarding antibiotic resistance pattern, horizontal gene transfer (HGT) and genetic support. OXA-484 differs by the amino acid substitution 214G compared to the most closely related variants OXA-181 (214R) and OXA-232 (214S). The bla OXA - 484 was carried on a self-transmissible 51.5 kb IncX3 plasmid (pOXA-484) showing high sequence similarity with plasmids harboring bla OXA - 181. Intraspecies and intergenus HGT of pOXA-484 to different recipients occurred at low frequencies of 1.4 × 10-7 to 2.1 × 10-6. OXA-484 increased MICs of temocillin and carbapenems similar to OXA-232 and OXA-244, but lower compared with OXA-48 and OXA-181. Hence, OXA-484 combines properties of OXA-181-like plasmid support and transferability as well as β-lactamase activity of OXA-232.

| S-EPMC8153228 | biostudies-literature

OXA-253, a variant of the carbapenem-hydrolyzing class D ?-lactamase OXA-143 in Acinetobacter baumannii.

Project description:The carbapenem-hydrolyzing class D ?-lactamase OXA-253 was identified in an Acinetobacter baumannii clinical isolate belonging to sequence type 113 (ST113) in Brazil. OXA-253 shares 93.8% amino acid identity with OXA-143. The blaOXA-253 gene is located on a ca. 20-kb plasmid. The genetic environment of the blaOXA-253 gene shares the highest identity with ubiquitous GR2 group plasmids usually carrying blaOXA-24/-40 genes.

| S-EPMC3993228 | biostudies-literature

Endemic carbapenem-resistant Pseudomonas aeruginosa with acquired metallo-beta-lactamase determinants in European hospital.

Project description:Acquired metallo-beta-lactamases (MBLs) can confer broad-spectrum beta-lactam resistance (including carbapenems) not reversible by conventional beta-lactamase inhibitors and are emerging resistance determinants of remarkable clinical importance. In 2001, multidrug-resistant Pseudomonas aeruginosa carrying bla(VIM) MBL genes were found to be widespread (approximately 20% of all P. aeruginosa isolates and 70% of the carbapenem-resistant isolates) at Trieste University Hospital. Clonal diversity and heterogeneity of resistance determinants (either bla(VIM-1)-like or bla(VIM-2)-like) were detected among MBL producers. This evidence is the first that acquired MBLs can rapidly emerge and establish a condition of endemicity in certain epidemiologic settings.

| S-EPMC3322785 | biostudies-literature

Hydrolytic mechanism of OXA-58 enzyme, a carbapenem-hydrolyzing class D ?-lactamase from Acinetobacter baumannii.

Project description:Carbapenem-hydrolyzing class D ?-lactamases (CHDLs) represent an emerging antibiotic resistance mechanism encountered among the most opportunistic Gram-negative bacterial pathogens. We report here the substrate kinetics and mechanistic characterization of a prominent CHDL, the OXA-58 enzyme, from Acinetobacter baumannii. OXA-58 uses a carbamylated lysine to activate the nucleophilic serine used for ?-lactam hydrolysis. The deacylating water molecule approaches the acyl-enzyme species, anchored at this serine (Ser-83), from the ?-face. Our data show that OXA-58 retains the catalytic machinery found in class D ?-lactamases, of which OXA-10 is representative. Comparison of the homology model of OXA-58 and the recently solved crystal structures of OXA-24 and OXA-48 with the OXA-10 crystal structure suggests that these CHDLs have evolved the ability to hydrolyze imipenem, an important carbapenem in clinical use, by subtle structural changes in the active site. These changes may contribute to tighter binding of imipenem to the active site and removal of steric hindrances from the path of the deacylating water molecule.

| S-EPMC3199476 | biostudies-literature

Evolution to carbapenem-hydrolyzing activity in noncarbapenemase class D ?-lactamase OXA-10 by rational protein design.

Project description:Class D ?-lactamases with carbapenemase activity are emerging as carbapenem-resistance determinants in gram-negative bacterial pathogens, mostly Acinetobacter baumannii and Klebsiella pneumoniae. Carbapenemase activity is an unusual feature among class D ?-lactamases, and the structural elements responsible for this activity remain unclear. Based on structural and molecular dynamics data, we previously hypothesized a potential role of the residues located in the short-loop connecting strands ?5 and ?6 (the ?5-?6 loop) in conferring the carbapenemase activity of the OXA-48 enzyme. In this work, the narrow-spectrum OXA-10 class D ?-lactamase, which is unable to hydrolyze carbapenems, was used as a model to investigate the possibility of evolving carbapenemase activity by replacement of the ?5-?6 loop with those present in three different lineages of class D carbapenemases (OXA-23, OXA-24, and OXA-48). Biological assays and kinetic measurements showed that all three OXA-10-derived hybrids acquired significant carbapenemase activity. Structural analysis of the OXA-10loop24 and OXA-10loop48 hybrids revealed no significant changes in the molecular fold of the enzyme, except for the orientation of the substituted ?5-?6 loops, which was reminiscent of that found in their parental enzymes. These results demonstrate the crucial role of the ?5-?6 loop in the carbapenemase activity of class D ?-lactamases, and provide previously unexplored insights into the mechanism by which these enzymes can evolve carbapenemase activity.

| S-EPMC3215043 | biostudies-literature

GES-18, a new carbapenem-hydrolyzing GES-Type β-lactamase from Pseudomonas aeruginosa that contains Ile80 and Ser170 residues.

Project description:A clinical isolate of Pseudomonas aeruginosa recovered from the lower respiratory tract of an 81-year-old patient hospitalized in Belgium was sent to the national reference center to determine its resistance mechanism. PCR sequencing identified a new GES variant, GES-18, which differs from the carbapenem-hydrolyzing enzyme GES-5 by a single amino acid substitution (Val80Ile, in the numbering according to Ambler) and from GES-1 by two substitutions (Val80Ile and Gly170Ser). Detailed kinetic characterization showed that GES-18 and GES-5 hydrolyze imipenem and cefoxitin with similar kinetic parameters and that GES-18 was less susceptible than GES-1 to classical β-lactamase inhibitors such as clavulanate and tazobactam. The overall structure of GES-18 is similar to the solved structures of GES-1 and GES-2, the Val80Ile and Gly170Ser substitutions causing only subtle local rearrangements. Notably, the hydrolytic water molecule and the Glu166 residue were slightly displaced compared to their counterparts in GES-1. Our kinetic and crystallographic data for GES-18 highlight the pivotal role of the Gly170Ser substitution which distinguishes GES-5 and GES-18 from GES-1.

| S-EPMC3535894 | biostudies-literature

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