{"entity": "researcher", "timestamp": "2026-05-19T07:12:46.412Z", "family": "Bester", "given": "Linda A", "initials": "LA", "orcid": "0000-0001-5726-681X", "affiliations": ["School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Durban 4000, South Africa."], "links": {"self": {"href": "https://publications.scilifelab.se/researcher/15b4bc949845434a9b612be0e28764a5.json"}, "display": {"href": "https://publications.scilifelab.se/researcher/15b4bc949845434a9b612be0e28764a5"}}, "publications": [{"entity": "publication", "iuid": "f8b2aad10ba84e868680d663819912c7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f8b2aad10ba84e868680d663819912c7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f8b2aad10ba84e868680d663819912c7"}}, "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.scilifelab.se/researcher/249183863e6842a59f3b2bba5c3d0670.json"}}, {"family": "Shungube", "given": "Mbongeni", "initials": "M"}, {"family": "Gouws", "given": "Arnoldus C", "initials": "AC", "orcid": "0000-0002-9848-719X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba06527dc4bd4d54b7ccf4db223f0691.json"}}, {"family": "Peters", "given": "Byron K", "initials": "BK"}, {"family": "Rajbongshi", "given": "Kamal K", "initials": "KK", "orcid": "0000-0003-0128-663X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b42da27a8b384a6684037107d0a158ca.json"}}, {"family": "Baijnath", "given": "Sooraj", "initials": "S", "orcid": "0000-0001-7860-1779", "researcher": {"href": "https://publications.scilifelab.se/researcher/a918cd14121f40bf88ad33082921e5c2.json"}}, {"family": "Mdanda", "given": "Sipho", "initials": "S", "orcid": "0000-0003-0146-0538", "researcher": {"href": "https://publications.scilifelab.se/researcher/564e56b376b04f2d996a425c16013a77.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.scilifelab.se/researcher/15b4bc949845434a9b612be0e28764a5.json"}}, {"family": "Singh", "given": "Sanil D", "initials": "SD"}, {"family": "Chuturgoon", "given": "Anil", "initials": "A", "orcid": "0000-0003-4649-4133", "researcher": {"href": "https://publications.scilifelab.se/researcher/f96bfd695ee44484ad9b87f9ef4e76a0.json"}}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.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.scilifelab.se/researcher/578365860e2b45b1aa8004d88e2f311c.json"}}, {"family": "Govender", "given": "Thavendran", "initials": "T", "orcid": "0000-0003-2511-2503", "researcher": {"href": "https://publications.scilifelab.se/researcher/88d16e433761470da735d3191d23a68a.json"}}, {"family": "Naicker", "given": "Tricia", "initials": "T", "orcid": "0000-0002-7134-6258", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe71fc16c2240af9919d68b69d7d652.json"}}], "type": "journal article", "published": "2023-03-23", "journal": {"title": "Antibiotics (Basel)", "issn": "2079-6382", "issn-l": null, "volume": "12", "issue": "4", "pages": 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": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10135050"}, {"db": "pii", "key": "antibiotics12040633"}], "notes": [], "created": "2024-01-16T15:19:03.368Z", "modified": "2025-10-17T13:05:07.644Z"}]}