Tietgen, Manuela, Kramer, Jan S., Brunst, Steffen, Djahanschiri, Bardya ORCID: 0000-0002-6066-8315, Wohra, Sonali, Higgins, Paul G. ORCID: 0000-0001-8677-9454, Weidensdorfer, Marko, Riedel-Christ, Sara, Pos, Klaas M., Gonzaga, Aitor, Steglich, Matthias, Nuebel, Ulrich, Ebersberger, Ingo, Proschak, Ewgenij and Goettig, Stephan (2019). Identification of the novel class D beta-lactamase OXA-679 involved in carbapenem resistance in Acinetobacter calcoaceticus. J. Antimicrob. Chemother., 74 (6). S. 1494 - 1503. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2091

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Abstract

Objectives: The aim of this study was to characterize the Acinetobacter calcoaceticus clinical isolate AC_2117 with the novel carbapenem-hydrolysing class D beta-lactamase (CHDL) OXA-679. Methods: Identification of the species and beta-lactamases was verified by genome sequencing (PacBio) and phylogenetic analyses. Antibiotic susceptibility of AC_2117 and transformants harbouring cloned bla(OXA-679) was evaluated using antibiotic gradient strips and microbroth dilution. OXA-679 was purified heterologously and kinetic parameters were determined using spectrometry or isothermal titration calorimetry. The impact of OXA-679 production during imipenemtherapy was evaluated in the Galleria mellonella infection model. Results: Sequencing of the complete genome of the clinical A. calcoaceticus isolate AC_2117 identified a novel CHDL, termed OXA-679. This enzyme shared sequence similarity of 71% to each of the families OXA-143 and OXA-24/40. Phylogenetic analyses revealed that OXA-679 represents a member of a new OXA family. Cloning and expression of bla(OXA-679) as well as measurement of kinetic parameters revealed the effective hydrolysis of carbapenems which resulted in reduced susceptibility to carbapenems in Escherichia coli and A. calcoaceticus, and high-level carbapenem resistance in Acinetobacter baumannii. Infection of larvae of G. mellonella with a sublethal dose of bla(OXA-679)-expressing A. baumannii could not be cured by high-dose imipenemtherapy, indicating carbapenem resistance in vivo. Conclusions: We identified bla(OXA-679) in a clinical A. calcoaceticus isolate that represents a member of the new OXA-679 family and that conferred high-level carbapenem resistance in vitro and in vivo.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Tietgen, ManuelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kramer, Jan S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brunst, SteffenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Djahanschiri, BardyaUNSPECIFIEDorcid.org/0000-0002-6066-8315UNSPECIFIED
Wohra, SonaliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Higgins, Paul G.UNSPECIFIEDorcid.org/0000-0001-8677-9454UNSPECIFIED
Weidensdorfer, MarkoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riedel-Christ, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pos, Klaas M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gonzaga, AitorUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Steglich, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nuebel, UlrichUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ebersberger, IngoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Proschak, EwgenijUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Goettig, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-138427
DOI: 10.1093/jac/dkz080
Journal or Publication Title: J. Antimicrob. Chemother.
Volume: 74
Number: 6
Page Range: S. 1494 - 1503
Date: 2019
Publisher: OXFORD UNIV PRESS
Place of Publication: OXFORD
ISSN: 1460-2091
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
IMIPENEM RESISTANCE; RPOB GENE; BAUMANNII; TREE; TOOLMultiple languages
Infectious Diseases; Microbiology; Pharmacology & PharmacyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13842

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