{
  "abstract": "Carbapenem-resistant Enterobacterales (CRE), including Escherichia coli and Klebsiella pneumoniae are increasingly common pathogens. Resistance in CRE is often associated with production of K. pneumoniae (KPC) carbapenemases. We report a structurally modified meropenem derivative, JDB-1-200 (i.e., 8-epi-meropenem, in which the stereochemistry of the C8 hydroxyl is inverted), displaying enhanced activity relative to meropenem against KPC-producing CRE. JDB-1-200 alone displayed superior activity (MICs of 0.5 to 1 mg/L, compared with >8 mg/L for meropenem) against several clinically relevant Enterobacterales, including KPC-producing K. pneumoniae and Citrobacter freundii. Crystallographic analysis of JDB-1-200 complexes with the E166Q deacylation-deficient KPC-2 mutant, compared with an analogous meropenem (8R-hydroxyl) complex, indicates that the improvement arises from the JDB 8S-hydroxyl group acting as a hydrogen-bond donor to the hydrolytic water, slowing acyl-enzyme hydrolysis, with similar interactions observed in a CTX-M-15:JDB-1-200 complex. Kinetic inhibition data for KPC-2 and CTX-M-15 indicate that JDB-1-200 could be used alone or alongside a β-lactamase inhibitor for effective CRE treatment.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Chemistry, Southern Methodist University, Dallas, Texas75275, United States.",
    "School of Cellular and Molecular Medicine, University of Bristol, Biomedical Sciences Building, University Walk, BristolBS8 1TD, U.K.",
    "Department of Life Sciences and Centre of Evolution, University of Bath, Claverton Down, BathBA2 7AY, U.K."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Taariq Hassan"
    },
    {
      "affs": [
        0
      ],
      "name": "Svanik Jaikumar"
    },
    {
      "affs": [
        0
      ],
      "name": "Diya Patel"
    },
    {
      "affs": [
        0
      ],
      "name": "Pojun Quan"
    },
    {
      "affs": [
        0
      ],
      "name": "Maidileyvis Castro Cabello"
    },
    {
      "affs": [
        0
      ],
      "name": "Jonathan E Cox",
      "orcid": "0009-0009-8033-3828"
    },
    {
      "affs": [
        0
      ],
      "name": "Md Mahbub Kabir Khan"
    },
    {
      "affs": [
        1
      ],
      "name": "James Spencer",
      "orcid": "0000-0002-4602-0571"
    },
    {
      "affs": [
        2
      ],
      "name": "Catherine L Tooke"
    },
    {
      "affs": [
        0
      ],
      "name": "John D Buynak",
      "orcid": "0000-0003-1007-791X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/3bsps7xneyg4p.bib",
  "cited_by": 0,
  "doi": "10.1021/acsinfecdis.6c00607",
  "fulltext_url": "https://europepmc.org/articles/PMC13660389",
  "id": "3bsps7xneyg4p",
  "issns": [
    "2373-8227"
  ],
  "landing_url": "https://europepmc.org/article/MED/42917105",
  "language": "eng",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1313|Antibiotic Resistance in Bacteria"
    ]
  ],
  "openalex": "W7211960528",
  "pdf_url": "https://europepmc.org/articles/PMC13660389?pdf=render",
  "pmcid": "PMC13660389",
  "pmid": "42917105",
  "published": "2026-10-01",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/3bsps7xneyg4p.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:36Z",
      "native_id": "MED:42917105",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42917105"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:1313|Antibiotic Resistance in Bacteria",
      "subfield": "general"
    }
  ],
  "title": "JDB-1-200, an Atypically Modified Carbapenem with Standalone In Vitro Activity against KPC-Producing Enterobacterales.",
  "title_text": "JDB-1-200, an Atypically Modified Carbapenem with Standalone In Vitro Activity against KPC-Producing Enterobacterales.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:36Z",
  "url": "https://research.draconitic.com/paper/3bsps7xneyg4p",
  "venue": "ACS infectious diseases",
  "versions": []
}