ArticlePLoS pathogens2020
Targeting bioenergetics is key to counteracting the drug-tolerant state of biofilm-grown bacteria.
Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- Overcoming Multidrug Resistance by Bacterial Efflux Pump Inhibitors in ClinicalAntibiotics (Basel, Switzerland) · 2026Article
- Sequential eradication of bacterial persisters: integrating phytochemical pharmacology with microenvironment-responsive delivery strategies.Frontiers in microbiology · 2026Review
- Adaptation to cinnamaldehyde shapesJournal of bacteriology · 2025Article
- Synthesis and Evaluation of Pyridine-Based Antibacterial Agents that Inhibit ATP Synthase inACS omega · 2025Article
- Quinoline ATP Synthase Inhibitors with Activity Against Multidrug Resistant Acinetobacter baumannii and Pseudomonas aeruginosa.ChemMedChem · 2025Article
- Fabrication of Multifunctional Three-Component Supramolecular Nano-Biscuits via Two Macrocycles-Involved Self-Assembly for Rice, Citrus and Kiwifruit Protections.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Bioenergetic suppression by redox-active metabolites promotes antibiotic tolerance inProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Repurposing promethazine hydrochloride to inhibit biofilm formation against Burkholderia thailandensis.Medical microbiology and immunology · 2024Article
- Mechanisms of antibiotic resistance inBiofilm · 2023Article
- Chenodeoxycholic Acid-Amikacin Combination Enhances Eradication of Staphylococcus aureus.Microbiology spectrum · 2023Article
- The Potential of Phenothiazines against Endodontic Pathogens: A Focus onAntibiotics (Basel, Switzerland) · 2022Article
- Contribution of Membrane Vesicle to Reprogramming of Bacterial Membrane Fluidity in Pseudomonas aeruginosa.mSphere · 2022Article
- Transcriptional Profiling of Pseudomonas aeruginosa Infections.Advances in experimental medicine and biology · 2022Review
- Nutrient Gradients Mediate Complex Colony-Level Antibiotic Responses in Structured Microbial Populations.Frontiers in microbiology · 2022Article
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Embedded in an extracellular matrix, biofilm-residing bacteria are protected from diverse physicochemical insults. In accordance, in the human host the general recalcitrance of biofilm-grown bacteria hinders successful eradication of chronic, biofilm-associated infections. In this study, we demonstrate that upon addition of promethazine, an FDA approved drug, antibiotic tolerance of in vitro biofilm-grown bacteria can be abolished. We show that following the addition of promethazine, diverse antibiotics are capable of efficiently killing biofilm-residing cells at minimal inhibitory concentrations. Synergistic effects could also be observed in a murine in vivo model system. PMZ was shown to increase membrane potential and interfere with bacterial respiration. Of note, antibiotic killing activity was elevated when PMZ was added to cells grown under environmental conditions that induce low intracellular proton levels. Our results imply that biofilm-grown bacteria avoid antibiotic killing and become tolerant by counteracting intracellular alkalization through the adaptation of metabolic and transport functions. Abrogation of antibiotic tolerance by interfering with the cell's bioenergetics promises to pave the way for successful eradication of biofilm-associated infections. Repurposing promethazine as a biofilm-sensitizing drug has the potential to accelerate the introduction of new treatments for recalcitrant, biofilm-associated infections into the clinic.
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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.