To Be or Not to Be an OXA-48 Carbapenemase
Since the first description of OXA-48, more than forty variants have been recovered from <i>Enterobacterales</i> isolates. Whereas some OXA-48-related enzymes have been reported as conferring similar resistance patterns, namely, the hydrolysis of carbapenems and penicillins with very wea...
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MDPI AG
2022-01-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/10/2/258 |
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| author | Laura Dabos Saoussen Oueslati Sandrine Bernabeu Rémy A. Bonnin Laurent Dortet Thierry Naas |
| author_facet | Laura Dabos Saoussen Oueslati Sandrine Bernabeu Rémy A. Bonnin Laurent Dortet Thierry Naas |
| author_sort | Laura Dabos |
| collection | DOAJ |
| description | Since the first description of OXA-48, more than forty variants have been recovered from <i>Enterobacterales</i> isolates. Whereas some OXA-48-related enzymes have been reported as conferring similar resistance patterns, namely, the hydrolysis of carbapenems and penicillins with very weak or almost no activity against expanded-spectrum cephalosporins, some have reduced carbapenem and temocillin hydrolysis, and others hydrolyze expanded-spectrum cephalosporins and carbapenems only marginally. With such drastic differences in the hydrolytic profile, especially of carbapenems, it becomes urgent to establish hydrolytic cutoffs in order to determine when an OXA-48-like enzyme may be considered as a carbapenemase or not. With this aim, the coefficient of activity for imipenem (<i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub>) was determined for a total of 30 enzymes, including OXA-48, OXA-48-like natural variants, and OXA-48 synthetic mutants. In addition, six different methods for the detection of carbapenemase-producers were performed. The coefficients of activity for imipenem for all the different enzymes went from 550 mM<sup>−1</sup>·s<sup>−1</sup> to 0.02 mM<sup>−1</sup>·s<sup>−1</sup>. In order to match the coefficient of activity results with the biochemical confirmatory tests, we suggest the value of 0.27 mM<sup>−1</sup>·s<sup>−1</sup> as the cutoff above which an OXA-48 variant may be considered a carbapenem-hydrolyzing enzyme. |
| first_indexed | 2024-03-09T21:23:25Z |
| format | Article |
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| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-09T21:23:25Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-223cfc7c5076402a9a71e1244334c3572023-11-23T21:13:18ZengMDPI AGMicroorganisms2076-26072022-01-0110225810.3390/microorganisms10020258To Be or Not to Be an OXA-48 CarbapenemaseLaura Dabos0Saoussen Oueslati1Sandrine Bernabeu2Rémy A. Bonnin3Laurent Dortet4Thierry Naas5Team “Resist” UMR1184 “Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)”, INSERM, Université Paris-Saclay, CEA, LabEx LERMIT, Faculty of Medicine, 94270 Le Kremlin-Bicêtre, FranceTeam “Resist” UMR1184 “Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)”, INSERM, Université Paris-Saclay, CEA, LabEx LERMIT, Faculty of Medicine, 94270 Le Kremlin-Bicêtre, FranceTeam “Resist” UMR1184 “Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)”, INSERM, Université Paris-Saclay, CEA, LabEx LERMIT, Faculty of Medicine, 94270 Le Kremlin-Bicêtre, FranceTeam “Resist” UMR1184 “Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)”, INSERM, Université Paris-Saclay, CEA, LabEx LERMIT, Faculty of Medicine, 94270 Le Kremlin-Bicêtre, FranceTeam “Resist” UMR1184 “Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)”, INSERM, Université Paris-Saclay, CEA, LabEx LERMIT, Faculty of Medicine, 94270 Le Kremlin-Bicêtre, FranceTeam “Resist” UMR1184 “Immunology of Viral, Auto-Immune, Hematological and Bacterial Diseases (IMVA-HB)”, INSERM, Université Paris-Saclay, CEA, LabEx LERMIT, Faculty of Medicine, 94270 Le Kremlin-Bicêtre, FranceSince the first description of OXA-48, more than forty variants have been recovered from <i>Enterobacterales</i> isolates. Whereas some OXA-48-related enzymes have been reported as conferring similar resistance patterns, namely, the hydrolysis of carbapenems and penicillins with very weak or almost no activity against expanded-spectrum cephalosporins, some have reduced carbapenem and temocillin hydrolysis, and others hydrolyze expanded-spectrum cephalosporins and carbapenems only marginally. With such drastic differences in the hydrolytic profile, especially of carbapenems, it becomes urgent to establish hydrolytic cutoffs in order to determine when an OXA-48-like enzyme may be considered as a carbapenemase or not. With this aim, the coefficient of activity for imipenem (<i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub>) was determined for a total of 30 enzymes, including OXA-48, OXA-48-like natural variants, and OXA-48 synthetic mutants. In addition, six different methods for the detection of carbapenemase-producers were performed. The coefficients of activity for imipenem for all the different enzymes went from 550 mM<sup>−1</sup>·s<sup>−1</sup> to 0.02 mM<sup>−1</sup>·s<sup>−1</sup>. In order to match the coefficient of activity results with the biochemical confirmatory tests, we suggest the value of 0.27 mM<sup>−1</sup>·s<sup>−1</sup> as the cutoff above which an OXA-48 variant may be considered a carbapenem-hydrolyzing enzyme.https://www.mdpi.com/2076-2607/10/2/258<i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub>coefficient of activitycarbapenem-hydrolysisOXA-48-likeconfirmatory tests |
| spellingShingle | Laura Dabos Saoussen Oueslati Sandrine Bernabeu Rémy A. Bonnin Laurent Dortet Thierry Naas To Be or Not to Be an OXA-48 Carbapenemase Microorganisms <i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub> coefficient of activity carbapenem-hydrolysis OXA-48-like confirmatory tests |
| title | To Be or Not to Be an OXA-48 Carbapenemase |
| title_full | To Be or Not to Be an OXA-48 Carbapenemase |
| title_fullStr | To Be or Not to Be an OXA-48 Carbapenemase |
| title_full_unstemmed | To Be or Not to Be an OXA-48 Carbapenemase |
| title_short | To Be or Not to Be an OXA-48 Carbapenemase |
| title_sort | to be or not to be an oxa 48 carbapenemase |
| topic | <i>k</i><sub>cat</sub>/<i>K</i><sub>m</sub> coefficient of activity carbapenem-hydrolysis OXA-48-like confirmatory tests |
| url | https://www.mdpi.com/2076-2607/10/2/258 |
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