ArticleScientific reports2019
A permeability-increasing drug synergizes with bacterial efflux pump inhibitors and restores susceptibility to antibiotics in multi-drug resistant Pseudomonas aeruginosa strains.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 86 citations in OpenAlex.
- Biosynthesis of Silver and Gold Nanoparticles using Inonotus obliquus: A strategy for Antimicrobial, Antioxidant and Cytotoxic Applications.Applied biochemistry and biotechnology · 2026Article
- Potential of Antimicrobial Peptide Synergies for Combating Infectious Diseases in Aquaculture: A Review.Animals : an open access journal from MDPI · 2026Review
- Overcoming Multidrug Resistance by Bacterial Efflux Pump Inhibitors in ClinicalAntibiotics (Basel, Switzerland) · 2026Article
- Phylogenomic and phenotypic profiling of carbapenem-resistantMicrobial genomics · 2026Article
- Broadly Defined Antibiotic Adjuvants forThe Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026Review
- Resistance breakers: a novel approach to tackle biofilm associated infections and antimicrobial resistance.Frontiers in microbiology · 2026Review
- From Laboratory to Clinic: Translational Medicine Paradigm of Polymyxin B Nanopreparations for Overcoming Drug-Resistant Bacterial Infections.International journal of nanomedicine · 2026Review
- Human vaginal Lactobacillus Jensenii -derived (-)-Terpinen-4-ol restores antibiotic sensitivity by inhibiting efflux pumps in drug resistant E. coli and K. pneumoniae.Scientific reports · 2025Article
- Human neutrophil α-defensin HNP1 interacts with bacterial OmpA to promote Acinetobacter baumannii biofilm formation.Nature communications · 2025Article
- Article
- Mechanical stability of individual bacterial cells under different osmotic pressure conditions: a nanoindentation study ofBeilstein journal of nanotechnology · 2025Article
- Bioluminescent Pseudomonas aeruginosa and Escherichia coli for whole-cell screening of antibacterial and adjuvant compounds.Scientific reports · 2024Article
- PA-Win2: In Silico-Based Discovery of a Novel Peptide with Dual Antibacterial and Anti-Biofilm Activity.Antibiotics (Basel, Switzerland) · 2024Article
- Antimicrobial peptide-based strategies to overcome antimicrobial resistance.Archives of microbiology · 2024Review
- Investigation of the role of Cremophor RH 40 and Cremophor EL in the inhibition of efflux pump ofHeliyon · 2024Article
- Efflux pump inhibitor, phenylalanine-arginine beta-naphthylamide analog potentiates the activity of 5-O-mycaminosyltylonolide for multi-drug resistant Pseudomonas aeruginosa.The Journal of antibiotics · 2024Article
- Heavy Metals as Catalysts in the Evolution of Antimicrobial Resistance and the Mechanisms Underpinning Co-selection.Current microbiology · 2024Review
- Polymyxin B nonapeptide potentiates the eradication of Gram-negative bacterial persisters.Microbiology spectrum · 2024Article
- Types and Mechanisms of Efflux Pump Systems and the Potential of Efflux Pump Inhibitors in the Restoration of Antimicrobial Susceptibility, with a Special Reference toPathogens (Basel, Switzerland) · 2024Review
- Ciprofloxacin-Loaded, pH-Responsive PAMAM-Megamers Functionalized with S-Nitrosylated Hyaluronic Acid Support Infected Wound Healing in Mice without Inducing Antibiotic Resistance.Advanced healthcare materials · 2024Article
Corrections and comments
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Authors and funding
6 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Resistance to antibiotics poses a major global threat according to the World Health Organization. Restoring the activity of existing drugs is an attractive alternative to address this challenge. One of the most efficient mechanisms of bacterial resistance involves the expression of efflux pump systems capable of expelling antibiotics from the cell. Although there are efflux pump inhibitors (EPIs) available, these molecules are toxic for humans. We hypothesized that permeability-increasing antimicrobial peptides (AMPs) could lower the amount of EPI necessary to sensitize bacteria to antibiotics that are efflux substrates. To test this hypothesis, we measured the ability of polymyxin B nonapeptide (PMBN), to synergize with antibiotics in the presence of EPIs. Assays were performed using planktonic and biofilm-forming cells of Pseudomonas aeruginosa strains overexpressing the MexAB-OprM efflux system. Synergy between PMBN and EPIs boosted azithromycin activity by a factor of 2,133 and sensitized P. aeruginosa to all tested antibiotics. This reduced several orders of magnitude the amount of inhibitor needed for antibiotic sensitization. The selected antibiotic-EPI-PMBN combination caused a 10 million-fold reduction in the viability of biofilm forming cells. We proved that AMPs can synergize with EPIs and that this phenomenon can be exploited to sensitize bacteria to antibiotics.
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