ArticlePLoS biology2020
Combining antibiotics with antivirulence compounds can have synergistic effects and reverse selection for antibiotic resistance in Pseudomonas aeruginosa.
Article in PLoS biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers.
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76 citing papers in PubMed.
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- Antimicrobial Armageddon: The Professional Guide to Conquering Antibiotic Resistance.Probiotics and antimicrobial proteins · 2026Article
- Contezolid and polymyxin B nonapeptide combination reveals antibacterial synergy against multidrug-resistant Acinetobacter baumannii strains.BMC microbiology · 2026Article
- Klebsiella pneumoniae in the global AMR: resistance mechanisms and genomic adaptation.World journal of microbiology & biotechnology · 2026Review
- An anti-adhesive compound modulating the production of Staphylococcus aureus cell wall-anchored proteins.Nature communications · 2026Article
- Multiple virulence attenuating strategies against Pseudomonas aeruginosa: Natural, synthetic, and synergistic approaches.World journal of microbiology & biotechnology · 2026Review
- Biofilm-Host Immune Crosstalk at the Diabetic Foot Ulcer Interface: Molecular Mechanisms, Immune Evasion, and Next-Generation Anti-Biofilm Strategies.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Review
- PFK-158 enhances colistin efficacy against resistantFrontiers in veterinary science · 2026Article
- Inhibition ofACS omega · 2025Article
- Multifaceted quorum-sensing inhibiting activity of 3-(Benzo[d][1,3]dioxol-4-yl)oxazolidin-2-one mitigatesVirulence · 2025Article
- Ferroptosis and iron-based therapies inVirulence · 2025Review
- Pseudomonas aeruginosa: ecology, evolution, pathogenesis and antimicrobial susceptibility.Nature reviews. Microbiology · 2025Review
- Antivirulence drugs against Acinetobacter baumannii: where do they stand?World journal of microbiology & biotechnology · 2025Review
- Antibacterial activity and mechanistic insights of gallium-based nanoparticles: an emerging frontier in metal-based antimicrobials.RSC advances · 2025Review
- Inhibition ofbioRxiv : the preprint server for biology · 2025Article
- Breaking the Phalanx: Overcoming Bacterial Drug Resistance with Quorum Sensing Inhibitors that Enhance Therapeutic Activity of Antibiotics.bioRxiv : the preprint server for biology · 2025Article
- Unlocking Enhanced Efficacy of Aminoglycoside Antibiotics Against Pseudomonas aeruginosa.Microbial biotechnology · 2025Review
- Accurate Diagnosis ofAntibiotics (Basel, Switzerland) · 2025Article
- Bio-informed synthesis of marine-sourced indole derivatives: suppressing gram-negative bacteria biofilm and virulence.BMC biology · 2025Article
16 more citing papers are in PubMed but not listed here.
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5 authors.
Funding
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Abstract
Antibiotics are losing efficacy due to the rapid evolution and spread of resistance. Treatments targeting bacterial virulence factors have been considered as alternatives because they target virulence instead of pathogen viability, and should therefore exert weaker selection for resistance than conventional antibiotics. However, antivirulence treatments rarely clear infections, which compromises their clinical applications. Here, we explore the potential of combining antivirulence drugs with antibiotics against the opportunistic human pathogen Pseudomonas aeruginosa. We combined two antivirulence compounds (gallium, a siderophore quencher, and furanone C-30, a quorum sensing [QS] inhibitor) together with four clinically relevant antibiotics (ciprofloxacin, colistin, meropenem, tobramycin) in 9×9 drug concentration matrices. We found that drug-interaction patterns were concentration dependent, with promising levels of synergies occurring at intermediate drug concentrations for certain drug pairs. We then tested whether antivirulence compounds are potent adjuvants, especially when treating antibiotic resistant (AtbR) clones. We found that the addition of antivirulence compounds to antibiotics could restore growth inhibition for most AtbR clones, and even abrogate or reverse selection for resistance in five drug combination cases. Molecular analyses suggest that selection against resistant clones occurs when resistance mechanisms involve restoration of protein synthesis, but not when efflux pumps are up-regulated. Altogether, our work provides a first systematic analysis of antivirulence-antibiotic combinatorial treatments and suggests that such combinations have the potential to be both effective in treating infections and in limiting the spread of antibiotic resistance.
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