Generation and selection of antibodies for a novel immunochromatographic lateral flow test to rapidly identify OXA-23-like-mediated carbapenem resistance in Acinetobacter baumannii
INTRODUCTION: The spread of carbapenem-resistant Acinetobacter baumannii has led to a worldwide healthcare problem. Carbapenem resistance in A. baumannii is mainly mediated by the acquisition of the carbapenem-hydrolyzing oxacillinase OXA-23. The phenotypic detection of carbapenem-producing A. baumannii is challenging and time-consuming. Hence, there is an unmet medical need for reliable and rapid diagnostic tools to detect OXA-23-producing Acinetobacter isolates to enable successful patient management.
AIM: Development of an immunochromatographic lateral flow test (ICT) for the rapid and reliable detection of OXA-23-producing carbapenem-resistant Acinetobacter isolates.
METHODOLOGY: For the development of an antibody-based ICT, we generated anti-OXA-23 monoclonal antibodies (MoAbs) and screened them sequentially for their ability to bind native OXA-23. Selected OXA-23-specific MoAbs were tested in different combinations for their capacity to capture and detect OXA-23His6 by sandwich enzyme-linked immunosorbent assay (ELISA) and ICT. A well-characterized collection of carbapenem-resistant Acinetobacter isolates with defined carbapenem resistance mechanisms were used to evaluate the specificity of the final OXA-23 ICT prototype.
RESULTS: The antibody pairs best suited for the sandwich ELISA format did not match the best pairs in the ICT format selected during the development process of the final prototype OXA-23 ICT. This prototype was able to differentiate between OXA-23 subfamily-mediated carbapenem resistance and carbapenem-resistant Acinetobacter isolates overexpressing other OXAs with 100 % specificity and a turnaround time of 20 min from culture plate to result.
CONCLUSION: With this rapid detection assay one can save 12-48 h of diagnostic time, which could help avoid inappropriate use of carbapenems and enable earlier intervention to control the transmission of OXA-23-producing carbapenem-resistant Acinetobacter isolates to other patients and healthcare workers.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:68 |
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| Enthalten in: |
Journal of medical microbiology - 68(2019), 7 vom: 28. Juli, Seite 1021-1032 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mertins, Sonja [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.07.2019 Date Revised 11.07.2019 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1099/jmm.0.001015 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM298050684 |
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| 100 | 1 | |a Mertins, Sonja |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Generation and selection of antibodies for a novel immunochromatographic lateral flow test to rapidly identify OXA-23-like-mediated carbapenem resistance in Acinetobacter baumannii |
| 264 | 1 | |c 2019 | |
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| 500 | |a Date Completed 11.07.2019 | ||
| 500 | |a Date Revised 11.07.2019 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a INTRODUCTION: The spread of carbapenem-resistant Acinetobacter baumannii has led to a worldwide healthcare problem. Carbapenem resistance in A. baumannii is mainly mediated by the acquisition of the carbapenem-hydrolyzing oxacillinase OXA-23. The phenotypic detection of carbapenem-producing A. baumannii is challenging and time-consuming. Hence, there is an unmet medical need for reliable and rapid diagnostic tools to detect OXA-23-producing Acinetobacter isolates to enable successful patient management | ||
| 520 | |a AIM: Development of an immunochromatographic lateral flow test (ICT) for the rapid and reliable detection of OXA-23-producing carbapenem-resistant Acinetobacter isolates | ||
| 520 | |a METHODOLOGY: For the development of an antibody-based ICT, we generated anti-OXA-23 monoclonal antibodies (MoAbs) and screened them sequentially for their ability to bind native OXA-23. Selected OXA-23-specific MoAbs were tested in different combinations for their capacity to capture and detect OXA-23His6 by sandwich enzyme-linked immunosorbent assay (ELISA) and ICT. A well-characterized collection of carbapenem-resistant Acinetobacter isolates with defined carbapenem resistance mechanisms were used to evaluate the specificity of the final OXA-23 ICT prototype | ||
| 520 | |a RESULTS: The antibody pairs best suited for the sandwich ELISA format did not match the best pairs in the ICT format selected during the development process of the final prototype OXA-23 ICT. This prototype was able to differentiate between OXA-23 subfamily-mediated carbapenem resistance and carbapenem-resistant Acinetobacter isolates overexpressing other OXAs with 100 % specificity and a turnaround time of 20 min from culture plate to result | ||
| 520 | |a CONCLUSION: With this rapid detection assay one can save 12-48 h of diagnostic time, which could help avoid inappropriate use of carbapenems and enable earlier intervention to control the transmission of OXA-23-producing carbapenem-resistant Acinetobacter isolates to other patients and healthcare workers | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acinetobacter baumannii | |
| 650 | 4 | |a OXA-23 | |
| 650 | 4 | |a carbapenem resistance | |
| 650 | 4 | |a diagnostic | |
| 650 | 4 | |a immunochromatographic lateral flow test (ICT) | |
| 650 | 4 | |a oxacillinase | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Bacterial Proteins |2 NLM | |
| 650 | 7 | |a Carbapenems |2 NLM | |
| 650 | 7 | |a beta-Lactamases |2 NLM | |
| 650 | 7 | |a EC 3.5.2.6 |2 NLM | |
| 700 | 1 | |a Higgins, Paul G |e verfasserin |4 aut | |
| 700 | 1 | |a Rodríguez, María González |e verfasserin |4 aut | |
| 700 | 1 | |a Borlon, Céline |e verfasserin |4 aut | |
| 700 | 1 | |a Gilleman, Quentin |e verfasserin |4 aut | |
| 700 | 1 | |a Mertens, Pascal |e verfasserin |4 aut | |
| 700 | 1 | |a Seifert, Harald |e verfasserin |4 aut | |
| 700 | 1 | |a Krönke, Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Klimka, Alexander |e verfasserin |4 aut | |
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