pH-mediated potentiation of aminoglycosides kills bacterial persisters and eradicates in vivo biofilms
| Autor: | Frédéric Fischer, Jean-Marc Ghigo, Sylvie Létoffé, Christophe Beloin, David Lebeaux, Ashwini Chauhan, Hilde De Reuse |
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| Přispěvatelé: | Génétique des Biofilms, Institut Pasteur [Paris], Pathogenèse de Helicobacter, This work was supported by an Institut Pasteur grant and by the French government's Investissement d'Avenir Program, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant ANR-10-LABX-62-IBEID). D. L. was supported by a grant from the AXA Research Fund., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP) |
| Rok vydání: | 2014 |
| Předmět: |
MESH: Staphylococcus aureus/drug effects
MESH: Escherichia coli/drug effects MESH: Hydrogen-Ion Concentration Antibiotics medicine.disease_cause biofilm MESH: Biofilms/drug effects MESH: Drug Synergism MESH: Anti-Bacterial Agents/pharmacology MESH: Pseudomonas aeruginosa/drug effects Immunology and Allergy MESH: Staphylococcal Infections/prevention & control Central Venous Catheters MESH: Animals MESH: Escherichia coli Infections/drug therapy MESH: Gentamicins/pharmacology MESH: Gentamicins/administration & dosage Escherichia coli Infections MESH: Arginine/administration & dosage MESH: Catheter-Related Infections/drug therapy Aminoglycoside MESH: Escherichia coli Infections/prevention & control Drug Synergism Hydrogen-Ion Concentration Staphylococcal Infections 3. Good health Anti-Bacterial Agents Infectious Diseases Staphylococcus aureus MESH: Arginine/pharmacology Pseudomonas aeruginosa Gentamicin Drug Therapy Combination medicine.drug MESH: Central Venous Catheters/microbiology MESH: Rats medicine.drug_class Biology In Vitro Techniques MESH: Central Venous Catheters/adverse effects Arginine MESH: Catheter-Related Infections/prevention & control Microbiology In vivo MESH: Pseudomonas Infections/prevention & control medicine Escherichia coli Animals Pseudomonas Infections MESH: In Vitro Techniques MESH: Staphylococcal Infections/drug therapy persister proton motive force Biofilm biology.organism_classification [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology Rats MESH: Drug Therapy Combination Biofilms Catheter-Related Infections aminoglycoside MESH: Pseudomonas Infections/drug therapy Gentamicins Bacteria |
| Zdroj: | Journal of Infectious Diseases Journal of Infectious Diseases, Oxford University Press (OUP), 2014, 210 (9), pp.1357-1366. ⟨10.1093/infdis/jiu286⟩ Journal of Infectious Diseases, 2014, 210 (9), pp.1357-1366. ⟨10.1093/infdis/jiu286⟩ |
| ISSN: | 1537-6613 0022-1899 |
| DOI: | 10.1093/infdis/jiu286⟩ |
| Popis: | International audience; BACKGROUND: Limitations in treatment of biofilm-associated bacterial infections are often due to subpopulation of persistent bacteria (persisters) tolerant to high concentrations of antibiotics. Based on the increased aminoglycoside efficiency under alkaline conditions, we studied the combination of gentamicin and the clinically compatible basic amino acid L-arginine against planktonic and biofilm bacteria both in vitro and in vivo. METHODS: Using Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli bioluminescent strains, we studied the combination of L-arginine and gentamicin against planktonic persisters through time-kill curves of late stationary-phase cultures. In vitro biofilm tolerance towards gentamicin was assessed using PVC 96 well-plates assays. Efficacy of gentamicin as antibiotic lock treatment (ALT) at 5 mg/mL at different pH was evaluated in vivo using a model of totally implantable venous access port (TIVAP) surgically implanted in rats. RESULTS: We demonstrated that a combination of gentamicin and the clinically compatible basic amino acid L-arginine increases in vitro planktonic and biofilm susceptibility to gentamicin, with 99% mortality amongst clinically relevant pathogens, i.e. S. aureus, E. coli and P. aeruginosa persistent bacteria. Moreover, although gentamicin local treatment alone showed poor efficacy in a clinically relevant in vivo model of catheter-related infection, gentamicin supplemented with L-arginine led to complete, long-lasting eradication of S. aureus and E. coli biofilms, when used locally. CONCLUSION: Given that intravenous administration of L-arginine to human patients is well tolerated, combined use of aminoglycoside and the non-toxic adjuvant L-arginine as catheter lock solution could constitute a new option for the eradication of pathogenic biofilms. |
| Databáze: | OpenAIRE |
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