ArticleAntimicrobial agents and chemotherapy2015
Profiling of β-lactam selectivity for penicillin-binding proteins in Streptococcus pneumoniae D39.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 116 citations in OpenAlex.
- De novo generation and computational screening of dual-targeting short peptide inhibitors against PBP2b and PBP2x in drug-resistant Streptococcus Pneumoniae.Molecular diversity · 2026Article
- Molecular characterization and correlation with β-lactam resistance of penicillin-binding protein2x, 2b, and 1a ofMicrobiology spectrum · 2026Article
- Peptide Mimetic Platform for Activity Profiling of Mycobacterial l,d-Transpeptidases.Biochemistry · 2026Article
- Methicillin treatment reveals that FtsZ phosphorylation influences the cell division ofPNAS nexus · 2026Article
- Resistance of Uropathogens to Tebipenem: An Analysis of the Evidence from In Vitro Antimicrobial Susceptibility Studies.Microorganisms · 2026Review
- Structural and Dynamics Analyses of β-Lactam Inhibition ofACS chemical biology · 2026Article
- Activity Profiling of Mycobacterial L,D-Transpeptidases.bioRxiv : the preprint server for biology · 2026Article
- Target Fidelity and Failure: Structure-Activity Relationship of High-Molecular-Mass Penicillin-Binding Proteins (HMM-PBPs) in RefractoryAntibiotics (Basel, Switzerland) · 2026Article
- Antibacterial Benzimidazole-2-Methanamines as Allosteric Modulators ofJournal of medicinal chemistry · 2026Article
- Repurposing the angiotensin II receptor blocker valsartan to inhibit penicillin-binding protein 3 and its mutants inFrontiers in bioinformatics · 2026Article
- Molecular Dynamics Simulations Demonstrate Reduced Antibiotic Affinity to Mirror Bacterial Targets.Computational and structural biotechnology journal · 2026Article
- The effect of MurM and a branched cell wall structure on penicillin resistance inJournal of bacteriology · 2025Article
- Specific variants inMicrobiology spectrum · 2025Article
- Transient inhibition of cell division in competent pneumococcal cells results from deceleration of the septal peptidoglycan complex.Nature communications · 2025Article
- Decoding the Penicillin-Binding Proteins with Activity-Based Probes.Accounts of chemical research · 2025Review
- Combining live fluorescence imaging with in situ cryoelectron tomography sheds light on the septation process inProceedings of the National Academy of Sciences of the United States of America · 2025Article
- A high-resolution screen identifies a preexisting beta-lactam that specifically treats Lyme disease in mice.Science translational medicine · 2025Article
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- Elongasome core proteins and class A PBP1a display zonal, processive movement at the midcell ofProceedings of the National Academy of Sciences of the United States of America · 2024Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Selective fluorescent β-lactam chemical probes enable the visualization of the transpeptidase activity of penicillin-binding proteins (PBPs) at different stages of bacterial cell division. To facilitate the development of new fluorescent probes for PBP imaging, we evaluated 20 commercially available β-lactams for selective PBP inhibition in an unencapsulated derivative of the D39 strain of Streptococcus pneumoniae. Live cells were treated with β-lactam antibiotics at different concentrations and subsequently incubated with Bocillin FL (Boc-FL; fluorescent penicillin) to saturate uninhibited PBPs. Fluorophore-labeled PBPs were visualized by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and fluorescence scanning. Among 20 compounds tested, carbapenems (doripenem and meropenem) were coselective for PBP1a, PBP2x, and PBP3, while six of the nine penicillin compounds were coselective for PBP2x and PBP3. In contrast, the seven cephalosporin compounds tested display variability in their PBP-binding profiles. Three cephalosporin compounds (cefoxitin, cephalexin, and cefsulodin) and the monobactam aztreonam exhibited selectivity for PBP3, while only cefuroxime (a cephalosporin) was selective for PBP2x. Treatment of S. pneumoniae cultures with a sublethal concentration of cefuroxime that inhibited 60% of PBP2x activity and less than 20% of the activity of other PBPs resulted in formation of elongated cells. In contrast, treatment of S. pneumoniae cultures with concentrations of aztreonam and cefoxitin that inhibited up to 70% of PBP3 activity and less than 30% of other PBPs resulted in no discernible morphological changes. Additionally, correlation of the MIC and IC50s for each PBP, with the exception of faropenem, amdinocillin (mecillinam), and 6-APA, suggests that pneumococcal growth inhibition is primarily due to the inhibition of PBP2x.
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