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Preferred beta-lactone synthesis can explain high rate of false-negative results in the detection of OXA-48-like carbapenemases
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SYSNO ASEP 0566655 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Preferred beta-lactone synthesis can explain high rate of false-negative results in the detection of OXA-48-like carbapenemases Tvůrce(i) Studentová, V. (CZ)
Sudová, V. (CZ)
Bitar, I. (CZ)
Pašková, V. (CZ)
Moravec, J. (CZ)
Pompach, Petr (MBU-M) RID, ORCID
Volný, Michael (MBU-M) ORCID
Novák, Petr (MBU-M) RID, ORCID
Hrabák, J. (CZ)Číslo článku 22235 Zdroj.dok. Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 12, č. 1 (2022)Poč.str. 12 s. Jazyk dok. eng - angličtina Země vyd. DE - Německo Klíč. slova antibiotic resistance ; beta lactone ; carbapenems ; gram-negative bacteria ; mass spectrometry Vědní obor RIV EE - Mikrobiologie, virologie Obor OECD Microbiology CEP NV19-05-00541 GA MZd - Ministerstvo zdravotnictví LX22NPO5103 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora MBU-M - RVO:61388971 UT WOS 000965605400070 EID SCOPUS 85144637995 DOI 10.1038/s41598-022-26735-5 Anotace The resistance to carbapenems is usually mediated by enzymes hydrolyzing β-lactam ring. Recently, an alternative way of the modification of the antibiotic, a β-lactone formation by OXA-48-like enzymes, in some carbapenems was identified. We focused our study on a deep analysis of OXA-48-like-producing Enterobacterales, especially strains showing poor hydrolytic activity. In this study, well characterized 74 isolates of Enterobacterales resistant to carbapenems were used. Carbapenemase activity was determined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), liquid chromatography/mass spectrometry (LC–MS), Carba-NP test and modified Carbapenem Inactivation Method (mCIM). As meropenem-derived β-lactone possesses the same molecular weight as native meropenem (MW 383.46 g/mol), β-lactonization cannot be directly detected by MALDI-TOF MS. In the spectra, however, the peaks of m/z = 340.5 and 362.5 representing decarboxylated β-lactone and its sodium adduct were detected in 25 out of 35 OXA-48-like producers. In the rest 10 isolates, decarboxylated hydrolytic product (m/z = 358.5) and its sodium adduct (m/z = 380.5) have been detected. The peak of m/z = 362.5 was detected in 3 strains co-producing OXA-48-like and NDM-1 carbapenemases. The respective signal was identified in no strain producing class A or class B carbapenemase alone showing its specificity for OXA-48-like carbapenemases. Using LC–MS, we were able to identify meropenem-derived β-lactone directly according to the different retention time. All strains with a predominant β-lactone production showed negative results of Carba NP test. In this study, we have demonstrated that the strains producing OXA-48-like carbapenemases showing false-negative results using Carba NP test and MALDI-TOF MS preferentially produced meropenem-derived β-lactone. We also identified β-lactone-specific peak in MALDI-TOF MS spectra and demonstrated the ability of LC–MS to detect meropenem-derived β-lactone. Pracoviště Mikrobiologický ústav Kontakt Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231 Rok sběru 2023 Elektronická adresa https://www.nature.com/articles/s41598-022-26735-5
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