{"entity": "publication", "iuid": "d0441c481f5b42248a0bfb194f1bd1ea", "timestamp": "2026-09-30T23:39:34.734Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/d0441c481f5b42248a0bfb194f1bd1ea.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/d0441c481f5b42248a0bfb194f1bd1ea"}}, "title": "Neutralizing Carbapenem Resistance by Co-Administering Meropenem with Novel \u03b2-Lactam-Metallo-\u03b2-Lactamase Inhibitors.", "authors": [{"family": "Reddy", "given": "Nakita", "initials": "N"}, {"family": "Girdhari", "given": "Letisha", "initials": "L", "orcid": "0000-0001-5841-2735", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/74d106eb83ef42fea7dc909edcde6337.json"}}, {"family": "Shungube", "given": "Mbongeni", "initials": "M"}, {"family": "Gouws", "given": "Arnoldus C", "initials": "AC", "orcid": "0000-0002-9848-719X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/8d278f9155da4134851f9e558b8d9f10.json"}}, {"family": "Peters", "given": "Byron K", "initials": "BK"}, {"family": "Rajbongshi", "given": "Kamal K", "initials": "KK", "orcid": "0000-0003-0128-663X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a1473c288f83416a823fb0b599f003b3.json"}}, {"family": "Baijnath", "given": "Sooraj", "initials": "S", "orcid": "0000-0001-7860-1779", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5cedc06c61074967821fce1c7dd757bb.json"}}, {"family": "Mdanda", "given": "Sipho", "initials": "S", "orcid": "0000-0003-0146-0538", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/41b500d95bee4b13aece4089931d649c.json"}}, {"family": "Ntombela", "given": "Thandokuhle", "initials": "T"}, {"family": "Arumugam", "given": "Thilona", "initials": "T"}, {"family": "Bester", "given": "Linda A", "initials": "LA", "orcid": "0000-0001-5726-681X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ae9f79bf3c964e98888e7a951d931eab.json"}}, {"family": "Singh", "given": "Sanil D", "initials": "SD"}, {"family": "Chuturgoon", "given": "Anil", "initials": "A", "orcid": "0000-0003-4649-4133", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3af870f9207f43e5ae3b802495214724.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/84789ce64d004c83919336cdf43c903e.json"}}, {"family": "Maguire", "given": "Glenn E M", "initials": "GEM"}, {"family": "Kruger", "given": "Hendrik G", "initials": "HG", "orcid": "0000-0003-0606-2053", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/88f669867879452ca86ab92c27fd285c.json"}}, {"family": "Govender", "given": "Thavendran", "initials": "T", "orcid": "0000-0003-2511-2503", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/77ef43839d9e476f95d124c9c34b81fa.json"}}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/f5b1b1625e8c43859647736baa3e83d9.json"}}], "type": "journal article", "published": "2023-03-23", "journal": {"title": "Antibiotics (Basel)", "issn": "2079-6382", "volume": "12", "issue": "4", "issn-l": null}, "abstract": "Virulent Enterobacterale strains expressing serine and metallo-\u03b2-lactamases (MBL) genes have emerged responsible for conferring resistance to hard-to-treat infectious diseases. One strategy that exists is to develop \u03b2-lactamase inhibitors to counter this resistance. Currently, serine \u03b2-lactamase inhibitors (SBLIs) are in therapeutic use. However, an urgent global need for clinical metallo-\u03b2-lactamase inhibitors (MBLIs) has become dire. To address this problem, this study evaluated BP2, a novel beta-lactam-derived \u03b2-lactamase inhibitor, co-administered with meropenem. According to the antimicrobial susceptibility results, BP2 potentiates the synergistic activity of meropenem to a minimum inhibitory concentration (MIC) of \u22641 mg/L. In addition, BP2 is bactericidal over 24 h and safe to administer at the selected concentrations. Enzyme inhibition kinetics showed that BP2 had an apparent inhibitory constant (Kiapp) of 35.3 \u00b5M and 30.9 \u00b5M against New Delhi Metallo-\u03b2-lactamase (NDM-1) and Verona Integron-encoded Metallo-\u03b2-lactamase (VIM-2), respectively. BP2 did not interact with glyoxylase II enzyme up to 500 \u00b5M, indicating specific (MBL) binding. In a murine infection model, BP2 co-administered with meropenem was efficacious, observed by the >3 log10 reduction in K. pneumoniae NDM cfu/thigh. Given the promising pre-clinical results, BP2 is a suitable candidate for further research and development as an (MBLI).", "doi": "10.3390/antibiotics12040633", "pmid": "37106995", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC10135050"}, {"db": "pii", "key": "antibiotics12040633"}], "notes": [], "created": "2026-09-23T12:56:17.230Z", "modified": "2026-09-23T12:56:17.460Z"}