TY - JOUR
T1 - OXA-427, a new plasmid-borne carbapenem-hydrolysing class D β-lactamase in Enterobacteriaceae
AU - Bogaerts, Pierre
AU - Naas, Thierry
AU - Saegeman, Veroniek
AU - Bonnin, Remy A.
AU - Schuermans, Annette
AU - Evrard, Stéphanie
AU - Bouchahrouf, Warda
AU - Jove, Thomas
AU - Tande, Didier
AU - De Bolle, Xavier
AU - Huang, Te Din
AU - Dortet, Laurent
AU - Glupczynski, Youri
N1 - Funding Information:
This work was presented in part at the 2015 ECCMID in Copenhagen (Poster P1307). This work was partially funded by Institut National d'Assurance Maladie-Invalidité (INAMI)/Rijksinstituut voor Ziekte-en Invaliditeitsverzekering (RIZIV) [Belgian Federal Government in the scope of the Belgian national reference center and a grant from the Institut National de la Santéet de la Recherche Médicale (INSERM) (U914) and by the Université Paris-Sud, France]. T. N. and L. D. are members of the Laboratory of Excellence Laboratoire d'Excellence en Recherche sur le Médicament et l'Innovation Thérapeutique (LabEx LERMIT) supported by a grant from Agence National de la Recherche (ANR) (ANR-10-LABX-33)
Publisher Copyright:
© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved.
PY - 2017/9/1
Y1 - 2017/9/1
N2 - Objectives: To describe a novel plasmid-borne class D carbapenemase (CHDL) named OXA-427 identified in several Enterobacteriaceae clinical isolates from nine patients in one Belgian hospital. Methods: OXA-427-producing isolates were analysed by an electrochemical imipenem hydrolysis method (BYG Carba test), Carba NP test, conventional phenotypic assays and by molecular methods (PCR, whole sequencing of the OXA-427-encoding plasmid and cloning). The antimicrobial resistance profile of OXA-427 was analysed by expression of the cloned gene in Escherichia coli DH10B and J53. Results: Eleven OXA-427-producing Enterobacteriaceae isolates of various species were identified from clinical specimens of nine patients between March 2012 and June 2014. OXA-427 shares only 22%-29% amino acid identity with OXA-48-like enzymes and other acquired CHDL (e.g. OXA-23, -24/40 and -58 of Acinetobacter spp.). Conversely, it appeared closely related to the chromosomal class D β-lactamase of Aeromonas media, Aeromonas hydrophila and Aeromonas sobria (99%, 89% and 77% of identity, respectively). When expressed in E. coli, OXA-427 hydrolysed imipenem and conferred resistance to extended-spectrum cephalosporins (mostly ceftazidime), penicillins including temocillin, and reduced susceptibility to carbapenems. The blaOXA-427 gene was located in a 45 kb resistance island on a 177 kb IncA/C plasmid. Conclusions: OXA-427 is a novel CHDL most closely related to chromosomal class D β-lactamase of A. media WS. It confers resistance to penicillins, ceftazidime and aztreonam and in some instances to carbapenems. OXA- 427, which is not detectable by classical molecular tests, caused a protracted outbreak in one university hospital over a 2 year period.
AB - Objectives: To describe a novel plasmid-borne class D carbapenemase (CHDL) named OXA-427 identified in several Enterobacteriaceae clinical isolates from nine patients in one Belgian hospital. Methods: OXA-427-producing isolates were analysed by an electrochemical imipenem hydrolysis method (BYG Carba test), Carba NP test, conventional phenotypic assays and by molecular methods (PCR, whole sequencing of the OXA-427-encoding plasmid and cloning). The antimicrobial resistance profile of OXA-427 was analysed by expression of the cloned gene in Escherichia coli DH10B and J53. Results: Eleven OXA-427-producing Enterobacteriaceae isolates of various species were identified from clinical specimens of nine patients between March 2012 and June 2014. OXA-427 shares only 22%-29% amino acid identity with OXA-48-like enzymes and other acquired CHDL (e.g. OXA-23, -24/40 and -58 of Acinetobacter spp.). Conversely, it appeared closely related to the chromosomal class D β-lactamase of Aeromonas media, Aeromonas hydrophila and Aeromonas sobria (99%, 89% and 77% of identity, respectively). When expressed in E. coli, OXA-427 hydrolysed imipenem and conferred resistance to extended-spectrum cephalosporins (mostly ceftazidime), penicillins including temocillin, and reduced susceptibility to carbapenems. The blaOXA-427 gene was located in a 45 kb resistance island on a 177 kb IncA/C plasmid. Conclusions: OXA-427 is a novel CHDL most closely related to chromosomal class D β-lactamase of A. media WS. It confers resistance to penicillins, ceftazidime and aztreonam and in some instances to carbapenems. OXA- 427, which is not detectable by classical molecular tests, caused a protracted outbreak in one university hospital over a 2 year period.
KW - Journal Article
KW - Carbapenems/metabolism
KW - Humans
KW - Middle Aged
KW - Drug Resistance, Multiple, Bacterial/genetics
KW - Enterobacteriaceae Infections/epidemiology
KW - Plasmids/genetics
KW - Anti-Bacterial Agents/metabolism
KW - Male
KW - Escherichia coli/drug effects
KW - Enterobacteriaceae/enzymology
KW - Hydrolysis
KW - Microbial Sensitivity Tests
KW - Belgium/epidemiology
KW - Bacterial Proteins/genetics
KW - Cloning, Molecular
KW - High-Throughput Nucleotide Sequencing
KW - beta-Lactamases/genetics
UR - http://www.scopus.com/inward/record.url?scp=85039982659&partnerID=8YFLogxK
U2 - 10.1093/jac/dkx184
DO - 10.1093/jac/dkx184
M3 - Article
C2 - 28859446
SN - 0305-7453
VL - 72
SP - 2469
EP - 2477
JO - The Journal of antimicrobial chemotherapy
JF - The Journal of antimicrobial chemotherapy
IS - 9
ER -