ArticleEMBO molecular medicine2024
Pyridylpiperazine efflux pump inhibitor boosts in vivo antibiotic efficacy against K. pneumoniae.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Designing Antibiotics with Inherent Resistance to Efflux as a Strategy to Revive Discovery against Multidrug-Resistant Pathogens.Journal of medicinal chemistry · 2026Article
- Genetic profiling of the tolC component of the acrAB-TolC efflux pump in clinical Klebsiella pneumoniae isolates: a cross-sectional study in Pontianak, Indonesia.Osong public health and research perspectives · 2026Article
- Molecular mechanism of transition-state inhibitors of bacterial antibiotic efflux pumps.npj antimicrobials and resistance · 2026Article
- WGS-based in silico analysis of clinically-associated Klebsiella pneumoniae genomes: insights into antimicrobial resistance, virulence determinants, and plasmid dynamics.Molecular genetics and genomics : MGG · 2026Article
- Optimizing the Antibiotic Potency and Metabolic Stability of Pyridomycin Using a Semisynthetic Approach.Journal of medicinal chemistry · 2026Article
- Breaking resistance: strategies for novel antibacterial therapeutic interventions.Molecular biology reports · 2026Review
- A review of research progress on periplasmic adaptor proteins in bacterial tripartite pumps.Frontiers in microbiology · 2026Review
- RND efflux pump inhibitor-like natural products as antibiotic adjuvants against multidrug-resistant gram-negative bacteria: a graded-evidence review.Frontiers in microbiology · 2026Review
- Breaking the outer membrane barrier: structure, targets, and antimicrobial strategies for Gram-negative bacteria.Frontiers in microbiology · 2026Review
- Exploring allosteric efflux pump inhibitors and the role of bacterial membrane potential in modulating drug resistance.Frontiers in microbiology · 2026Review
- Beyond antibiotic resistance: evidence for resistance-nodulation-division (RND) efflux pumps as virulence determinants.Microbiology and molecular biology reviews : MMBR · 2025Review
- Efflux-Mediated Resistance inAntibiotics (Basel, Switzerland) · 2025Review
- TolCV1 inhibition by NPPB rendersAntimicrobial agents and chemotherapy · 2025Article
- The poly (A) polymeraseFrontiers in microbiology · 2025Article
- Biological Evaluation and Computational Modelling Studies onCurrent pharmaceutical design · 2025Article
- Based on quorum sensing: reverse effect of traditional Chinese medicine on bacterial drug resistance mechanism.Frontiers in cellular and infection microbiology · 2025Review
- Structural and functional diversity of Resistance-Nodulation-Division (RND) efflux pump transporters with implications for antimicrobial resistance.Microbiology and molecular biology reviews : MMBR · 2024Review
- Extending the Potency and Lifespan of Antibiotics: Inhibitors of Gram-Negative Bacterial Efflux Pumps.ACS infectious diseases · 2024Review
- Molecular insights into the determinants of substrate specificity and efflux inhibition of the RND efflux pumps AcrB and AdeB.Microbiology (Reading, England) · 2024Review
Corrections and comments
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Authors and funding
19 authors.
Funding
Abstract
Antimicrobial resistance is a global problem, rendering conventional treatments less effective and requiring innovative strategies to combat this growing threat. The tripartite AcrAB-TolC efflux pump is the dominant constitutive system by which Enterobacterales like Escherichia coli and Klebsiella pneumoniae extrude antibiotics. Here, we describe the medicinal chemistry development and drug-like properties of BDM91288, a pyridylpiperazine-based AcrB efflux pump inhibitor. In vitro evaluation of BDM91288 confirmed it to potentiate the activity of a panel of antibiotics against K. pneumoniae as well as revert clinically relevant antibiotic resistance mediated by acrAB-tolC overexpression. Using cryo-EM, BDM91288 binding to the transmembrane region of K. pneumoniae AcrB was confirmed, further validating the mechanism of action of this inhibitor. Finally, proof of concept studies demonstrated that oral administration of BDM91288 significantly potentiated the in vivo efficacy of levofloxacin treatment in a murine model of K. pneumoniae lung infection.
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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.