ArticleClinical pharmacology and therapeutics2021
Combating Multidrug-Resistant Bacteria by Integrating a Novel Target Site Penetration and Receptor Binding Assay Platform Into Translational Modeling.
Article in Clinical pharmacology and therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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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.
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Who cites it
12 citing papers in PubMed, 12 citations in OpenAlex.
- Emergence of Klebsiella pneumoniae Carbapenemase-Producing K. pneumoniae with Penicillin-Binding Protein 3 Insertions, Taiwan, 2021.Emerging infectious diseases · 2026Review
- Translating Pharmacokinetic-Pharmacodynamic Principles Into Improved Methodology for Clinical Trials That Compare Intermittent With Prolonged Infusion of Beta-Lactam Antibiotics.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2025Article
- Enhancing the destruction ofFrontiers in cellular and infection microbiology · 2025Article
- Comprehensive stability analysis of 13 β-lactams and β-lactamase inhibitors inAntimicrobial agents and chemotherapy · 2024Article
- Next generation antibiotic combinations to combat pan-drug resistant Klebsiella pneumoniae.Scientific reports · 2024Article
- Drug Discovery in the Field of β-Lactams: An Academic Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Penicillin-Binding Protein 5/6 Acting as a Decoy Target in Pseudomonas aeruginosa Identified by Whole-Cell Receptor Binding and Quantitative Systems Pharmacology.Antimicrobial agents and chemotherapy · 2023Article
- PBP Target Profiling by β-Lactam and β-Lactamase Inhibitors in Intact Pseudomonas aeruginosa: Effects of the Intrinsic and Acquired Resistance Determinants on the Periplasmic Drug Availability.Microbiology spectrum · 2023Article
- Live-Cell Profiling of Penicillin-Binding Protein Inhibitors inACS infectious diseases · 2022Article
- Synthesis and Structure-Activity Relationship of Thioacetamide-Triazoles againstMolecules (Basel, Switzerland) · 2022Article
- Informing and Validating Translational Mechanism-Based Models for Antibiotics by Experimental and Computational Approaches.Clinical pharmacology and therapeutics · 2021Article
- Generating Genotype-Specific Aminoglycoside Combinations with Ceftazidime/Avibactam for KPC-ProducingAntimicrobial agents and chemotherapy · 2021Article
Corrections and comments
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Authors and funding
38 authors at 14 institutions in 6 countries.
Funding
Abstract
Multidrug-resistant bacteria are causing a serious global health crisis. A dramatic decline in antibiotic discovery and development investment by pharmaceutical industry over the last decades has slowed the adoption of new technologies. It is imperative that we create new mechanistic insights based on latest technologies, and use translational strategies to optimize patient therapy. Although drug development has relied on minimal inhibitory concentration testing and established in vitro and mouse infection models, the limited understanding of outer membrane permeability in Gram-negative bacteria presents major challenges. Our team has developed a platform using the latest technologies to characterize target site penetration and receptor binding in intact bacteria that inform translational modeling and guide new discovery. Enhanced assays can quantify the outer membrane permeability of β-lactam antibiotics and β-lactamase inhibitors using multiplex liquid chromatography tandem mass spectrometry. While β-lactam antibiotics are known to bind to multiple different penicillin-binding proteins (PBPs), their binding profiles are almost always studied in lysed bacteria. Novel assays for PBP binding in the periplasm of intact bacteria were developed and proteins identified via proteomics. To characterize bacterial morphology changes in response to PBP binding, high-throughput flow cytometry and time-lapse confocal microscopy with fluorescent probes provide unprecedented mechanistic insights. Moreover, novel assays to quantify cytosolic receptor binding and intracellular drug concentrations inform target site occupancy. These mechanistic data are integrated by quantitative and systems pharmacology modeling to maximize bacterial killing and minimize resistance in in vitro and mouse infection models. This translational approach holds promise to identify antibiotic combination dosing strategies for patients with serious infections.
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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.