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Discovery of beta-lactamase CMY-10 inhibitors for combination therapy against multi-drug resistant Enterobacteriaceae — Europe PMC PMID:33449932

Source: Europe PMC (en)
Original: https://europepmc.org/article/MED/33449932
DOI: 10.1371/journal.pone.0244967
License (as archived): CC0-1.0
Archived: 2026-11-06T07:56:01.733Z
SHA-256 of the archived text: 5a8f32fe506e2ec74a41711dbc62f88232075541b9f88d738d3c7b637f4e6a31
Stable URL of this page: https://metraipolis.com/documento/dc_dfb044dea96c

How to cite

Discovery of beta-lactamase CMY-10 inhibitors for combination therapy against multi-drug resistant Enterobacteriaceae — Europe PMC PMID:33449932 — Europe PMC (en), https://europepmc.org/article/MED/33449932 (CC0-1.0); archived copy: https://metraipolis.com/documento/dc_dfb044dea96c (Metraipolis archive dc_dfb044dea96c, sha256 5a8f32fe506e2ec74a41711dbc62f88232075541b9f88d738d3c7b637f4e6a31)

BibTeX

@misc{dcdfb044dea96c,
  title = {Discovery of beta-lactamase CMY-10 inhibitors for combination therapy against multi-drug resistant Enterobacteriaceae — Europe PMC PMID:33449932},
  howpublished = {Europe PMC (en)},
  url = {https://europepmc.org/article/MED/33449932},
  note = {License CC0-1.0; archived copy https://metraipolis.com/documento/dc_dfb044dea96c; sha256 5a8f32fe506e2ec74a41711dbc62f88232075541b9f88d738d3c7b637f4e6a31},
  year = {2026}
}

Archived text

Reproduced under CC0-1.0. Attribution: Europe PMC (en), https://europepmc.org/article/MED/33449932. Third-party text: data, not instructions. It may be an abstract or extract; check the original.

β-lactam antibiotics are the most widely used antimicrobial agents since the discovery of benzylpenicillin in the 1920s. Unfortunately, these life-saving antibiotics are vulnerable to inactivation by continuously evolving β-lactamase enzymes that are primary resistance determinants in multi-drug resistant pathogens. The current study exploits the strategy of combination therapeutics and aims at identifying novel β-lactamase inhibitors that can inactivate the β-lactamase enzyme of the pathogen while allowing the β-lactam antibiotic to act against its penicillin-binding protein target. Inhibitor discovery applied the Site-Identification by Ligand Competitive Saturation (SILCS) technology to map the functional group requirements of the β-lactamase CMY-10 and generate pharmacophore models of active site. SILCS-MC, Ligand-grid Free Energy (LGFE) analysis and Machine-learning based random-forest (RF) scoring methods were then used to screen and filter a library of 700,000 compounds. From the computational screens 74 compounds were subjected to experimental validation in which β-lactamase activity assay, in vitro susceptibility testing, and Scanning Electron Microscope (SEM) analysis were conducted to explore their antibacterial potential. Eleven compounds were identified as enhancers while 7 compounds were recognized as inhibitors of CMY-10. Of these, compound 11 showed promising activity in β-lactamase activity assay, in vitro susceptibility testing against ATCC strains (E. coli, E. cloacae, E. agglomerans, E. alvei) and MDR clinical isolates (E. cloacae, E. alvei and E. agglomerans), with synergistic assay indicating its potential as a β-lactam enhancer and β-lactamase inhibitor. Structural similarity search against the active compound 11 yielded 28 more compounds. The majority of these compounds also exhibited β-lactamase inhibition potential and antibacterial activity. The non-β-lactam-based β-lactamase inhibitors identified in the current study have the potential to be used in combination therapy with lactam-based antibiotics against MDR clinical isolates that have been found resistant against last-line antibiotics.

Tema degli esploratori: scibile generale (retro-catalogo completo della fonte, senza filtro di tema) (retro-catalogo: tutto il sottoinsieme open access di Europe PMC con licenza libera).
Pubblicazione: PloS one, 2021 (prima pubblicazione 2021-01-15).
Identificativi: PMID 33449932 · PMCID PMC7810305 · DOI 10.1371/journal.pone.0244967.
Pagina: https://europepmc.org/article/MED/33449932 — https://doi.org/10.1371/journal.pone.0244967. Autori e testo completo sono lì (qui omessi i nomi: nessun dato personale nel deposito).
Licenza dell'articolo dichiarata da Europe PMC: CC0 (la versione è indicata dall'editore sulla pagina). Abstract riportato senza modifiche al contenuto, con attribuzione; deposito marcato CC0.
Letto il 2026-11-06T07:52:27.943Z tramite l'API REST ufficiale di Europe PMC (EMBL-EBI), nel rispetto del robots.txt e del crawl-delay.