ArticlePhilosophical transactions of the Royal Society of London. Series B, Biological sciences2016
Antimicrobial combinations: Bliss independence and Loewe additivity derived from mechanistic multi-hit models.
Article in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed.
- Artificial intelligence catalyzes antimicrobial peptide design.Synthetic and systems biotechnology · 2027Review
- Dynamic hinge-motion of PfRIPR revealed by malaria invasion inhibitory antibodies.Nature communications · 2026Article
- Lactoferrin Displays Stimulating and Protective Effects on Newly Isolated Phage vB_Sau-E: A New Perspective for Treatment of Staphylococcal Skin Infections.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Natural-Compound Adjuvants Dismantle Candida Biofilms: Mechanisms, Design Rules, and Biofilm-Aware Pharmacology.Current microbiology · 2026Review
- Synergistic effects of colistin-based combinations against colistin and carbapenem-resistant Klebsiella pneumoniae isolated from nosocomial bloodstream infections.Scientific reports · 2025Article
- Synergistic Paradigms in Infection Control: A Review on Photodynamic Therapy as an Adjunctive Strategy to Antibiotics.ACS infectious diseases · 2025Review
- Therapeutic effect of pH responsive Magainin II modified azithromycin plus curcumin micelles in different depth models of MRSA infection.Scientific reports · 2025Article
- Resolving discrepancies between chimeric and multiplicative measures of higher-order epistasis.Nature communications · 2025Article
- Optimal Effective Concentration Combinations and synergy evaluations for binary antimicrobial combinationsFrontiers in microbiology · 2025Article
- The many dimensions of combination therapy: How to combine antibiotics to limit resistance evolution.Evolutionary applications · 2024Article
- Paclitaxel and Carboplatin in Combination with Low-intensity Pulsed Ultrasound for Glioblastoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Pyoverdine-antibiotic combination treatment: its efficacy and effects on resistance evolution inmicroLife · 2024Article
- Interactions of plumbagin with five common antibiotics against Staphylococcus aureus in vitro.PloS one · 2024Article
- Synergistic combinations ofFrontiers in pharmacology · 2024Article
- Novel Synergies and Isolate Specificities in the Drug Interaction Landscape of Mycobacterium abscessus.Antimicrobial agents and chemotherapy · 2023Article
- The pharmacokinetic-pharmacodynamic modelling framework as a tool to predict drug resistance evolution.Microbiology (Reading, England) · 2023Article
- Combining SNAPs with antibiotics shows enhanced synergistic efficacy against S. aureus and P. aeruginosa biofilms.NPJ biofilms and microbiomes · 2023Article
- The effect of combined knockdowns of Attacins on survival and bacterial load inFrontiers in immunology · 2023Article
- Sequential antibiotic therapy in the laboratory and in the patient.Journal of the Royal Society, Interface · 2023Article
- Repurposing Dimetridazole and Ribavirin to disarmFrontiers in microbiology · 2022Article
Corrections and comments
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5 authors.
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Abstract
Antimicrobial peptides (AMPs) and antibiotics reduce the net growth rate of bacterial populations they target. It is relevant to understand if effects of multiple antimicrobials are synergistic or antagonistic, in particular for AMP responses, because naturally occurring responses involve multiple AMPs. There are several competing proposals describing how multiple types of antimicrobials add up when applied in combination, such as Loewe additivity or Bliss independence. These additivity terms are defined ad hoc from abstract principles explaining the supposed interaction between the antimicrobials. Here, we link these ad hoc combination terms to a mathematical model that represents the dynamics of antimicrobial molecules hitting targets on bacterial cells. In this multi-hit model, bacteria are killed when a certain number of targets are hit by antimicrobials. Using this bottom-up approach reveals that Bliss independence should be the model of choice if no interaction between antimicrobial molecules is expected. Loewe additivity, on the other hand, describes scenarios in which antimicrobials affect the same components of the cell, i.e. are not acting independently. While our approach idealizes the dynamics of antimicrobials, it provides a conceptual underpinning of the additivity terms. The choice of the additivity term is essential to determine synergy or antagonism of antimicrobials.This article is part of the themed issue 'Evolutionary ecology of arthropod antimicrobial peptides'.
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