The increase in carbapenemase-producing (CPE), including metallo-β-lactamase (MBL) producers, is a severe global health concern. Thus, highly sensitive and specific methods for detecting MBL producers are needed. In this study, we tested the detectability of MBL-producing against three types of MBL inhibitors (sodium mercaptoacetate, SMA; ethylenediaminetetraacetic acid, EDTA; and dipicolinic acid, DPA) used in combination with a modified carbapenem inactivation method (mCIM). These inhibitor-combination mCIMs were tested against 129 CPE (IMP, 93; NDM, 11; KPC, 13; NMC, 1; OXA-48, 11) and 75 non-CPE. For evaluation of MBL inhibitors, we used two concentrations for each of the three inhibitors: DPA (200 and 300 mg l ), EDTA (5 and 10 mM), and SMA (1500 and 3000 mg l ). The overall sensitivities of SMA, EDTA and DPA were 97.1-99.0 %, 81.7-99.0 % and 88.5-96.2 %, respectively. Moreover, each method showed high specificity (99.0-100 %). Although inhibitor-combination mCIMs were highly sensitive and specific for the detection of MBL producers, we found that sensitivity was dependent on the concentration of inhibitors.
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http://dx.doi.org/10.1099/jmm.0.001073 | DOI Listing |
Antibiotics (Basel)
December 2024
Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, 00168 Rome, Italy.
Metallo-β-lactamases (MBLs) in and other Gram-negative organisms pose significant public health threats due to their association with multidrug resistance (MDR). Although aztreonam (AZT) can target MBL-producing organisms, its efficacy is compromised in organisms expressing additional β-lactamases that inactivate it. Combining AZT with the β-lactamase inhibitor avibactam (AVI) may restore its activity against MBL-producing isolates.
View Article and Find Full Text PDFAntibiotics (Basel)
December 2024
Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea.
Previously, we reported that 3--alkyl difluoroquercetins (di-F-Q) potentiates the antimicrobial activity of aztreonam (ATM) against metallo-β-lactamase (MBL)-producing through simultaneous inhibition of MBLs and efflux pumps. However, the ATM-potentiating activity of the 3--alkyl di-F-Q was observed only at high and potentially toxic concentrations (32 mg/L). As both MBLs and efflux pumps reside in the periplasm of Gram-negative bacteria, their inhibitors should accumulate in the periplasmic space.
View Article and Find Full Text PDFEur J Clin Microbiol Infect Dis
December 2024
Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science and Medicine, University of Fribourg, Chemin du Musée 18, Fribourg, CH-1700, Switzerland.
To evaluate the in-vitro activity of the novel commercially-available drugs, including meropenem-vaborbactam (MEV), ceftazidime-avibactam (CZA), ceftolozane-tazobactam (C/T), imipenem-relebactam (IPR) as well as cefiderocol (FDC), against carbapenem-resistant Pseudomonas spp. (CRP) isolates. All CRP isolates collected at the Swiss National Reference Laboratory (NARA) over the year 2022 (n = 170) have been included.
View Article and Find Full Text PDFOncogene
December 2024
Department of Hematology, the Second Xiangya Hospital; School of Life Sciences; Hunan Province Key Laboratory of Basic and Applied Hematology, Central South University, Changsha, Hunan, 410011, China.
Multiple myeloma (MM), the world's second most common hematologic malignancy, poses considerable clinical challenges due to its aggressive progression and resistance to therapy. Addressing these challenges requires a detailed understanding of the mechanisms driving MM initiation, progression, and therapeutic resistance. This study identifies the pseudokinase tribble homolog 3 (TRIB3) as a high-risk factor that promotes MM malignancy in vitro and in vivo.
View Article and Find Full Text PDFJ Phys Chem B
December 2024
EaStCHEM School of Chemistry, University of Edinburgh, Edinburgh EH9 3FJ, United Kingdom.
While relative binding free energy (RBFE) calculations using alchemical methods are routinely carried out for many pharmaceutically relevant protein targets, challenges remain. For example, open-source tools do not support the easy setup and simulation of metalloproteins, particularly when ligands directly coordinate to the metal site. Here, we evaluate the performance of RBFE methods for KPC-2, a serine-β-lactamase (SBL), and two nonbonded metal parameter setups for VIM-2, a metallo-β-lactamase (MBL) with two active site zinc ions.
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