ArticlePloS one2012
High-throughput screening for novel inhibitors of Neisseria gonorrhoeae penicillin-binding protein 2.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
16 citing papers in PubMed, 32 citations in OpenAlex.
- A penicillin-binding protein inhibitor series to target drug-resistant Neisseria gonorrhoeae.Nature microbiology · 2026Article
- Computational and Experimental Study of Metal-Organic Frameworks (MOFs) as Antimicrobial Agents againstACS applied materials & interfaces · 2025Article
- A new class of penicillin-binding protein inhibitors to address drug-resistantbioRxiv : the preprint server for biology · 2024Article
- Differential contribution of PBP occupancy and efflux on the effectiveness of β-lactams at their target site in clinical isolates of Neisseria gonorrhoeae.PLoS pathogens · 2024Article
- Development of phenyl-urea-based small molecules that target penicillin-binding protein 4.Chemical biology & drug design · 2024Article
- Chemical genetic approaches for the discovery of bacterial cell wall inhibitors.RSC medicinal chemistry · 2023Review
- Identification ofAntibiotics (Basel, Switzerland) · 2022Article
- Discovery of Pyrrolidine-2,3-diones as Novel Inhibitors ofAntibiotics (Basel, Switzerland) · 2021Article
- Fluorescent antibiotics for real-time tracking of pathogenic bacteria.Journal of pharmaceutical analysis · 2020Review
- On Column Binding a Real-Time Biosensor forMolecules (Basel, Switzerland) · 2020Article
- Influence of the α-Methoxy Group on the Reaction of Temocillin with Pseudomonas aeruginosa PBP3 and CTX-M-14 β-Lactamase.Antimicrobial agents and chemotherapy · 2019Article
- Future Prospects forAntibiotics (Basel, Switzerland) · 2018Review
- Glycosyltransferases and Transpeptidases/Penicillin-Binding Proteins: Valuable Targets for New Antibacterials.Antibiotics (Basel, Switzerland) · 2016Review
- Multicomponent mixtures for cryoprotection and ligand solubilization.Biotechnology reports (Amsterdam, Netherlands) · 2015Article
- Resistance to antibiotics targeted to the bacterial cell wall.Protein science : a publication of the Protein Society · 2014Review
- Inhibition of DD-peptidases by a specific trifluoroketone: crystal structure of a complex with the Actinomadura R39 DD-peptidase.Biochemistry · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The increasing prevalence of N. gonorrhoeae strains exhibiting decreased susceptibility to third-generation cephalosporins and the recent isolation of two distinct strains with high-level resistance to cefixime or ceftriaxone heralds the possible demise of β-lactam antibiotics as effective treatments for gonorrhea. To identify new compounds that inhibit penicillin-binding proteins (PBPs), which are proven targets for β-lactam antibiotics, we developed a high-throughput assay that uses fluorescence polarization (FP) to distinguish the fluorescent penicillin, Bocillin-FL, in free or PBP-bound form. This assay was used to screen a 50,000 compound library for potential inhibitors of N. gonorrhoeae PBP 2, and 32 compounds were identified that exhibited >50% inhibition of Bocillin-FL binding to PBP 2. These included a cephalosporin that provided validation of the assay. After elimination of compounds that failed to exhibit concentration-dependent inhibition, the antimicrobial activity of the remaining 24 was tested. Of these, 7 showed antimicrobial activity against susceptible and penicillin- or cephalosporin-resistant strains of N. gonorrhoeae. In molecular docking simulations using the crystal structure of PBP 2, two of these inhibitors docked into the active site of the enzyme and each mediate interactions with the active site serine nucleophile. This study demonstrates the validity of a FP-based assay to find novel inhibitors of PBPs and paves the way for more comprehensive high-throughput screening against highly resistant strains of N. gonorrhoeae. It also provides a set of lead compounds for optimization of anti-gonococcal agents.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.