pH-Mediated Potentiation of Aminoglycosides Kills Bacterial Persisters and Eradicates In Vivo Biofilms - Institut Pasteur Access content directly
Journal Articles Journal of Infectious Diseases Year : 2014

pH-Mediated Potentiation of Aminoglycosides Kills Bacterial Persisters and Eradicates In Vivo Biofilms

Abstract

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.
Fichier principal
Vignette du fichier
Post-Print_Lebeauxetal.JID.2014.pdf (1.81 Mo) Télécharger le fichier
Origin : Files produced by the author(s)
Loading...

Dates and versions

pasteur-01381819 , version 1 (17-11-2016)

Licence

Attribution - NonCommercial - ShareAlike

Identifiers

Cite

David Lebeaux, Ashwini Chauhan, Sylvie Létoffé, Frédéric Fischer, Hilde de Reuse, et al.. pH-Mediated Potentiation of Aminoglycosides Kills Bacterial Persisters and Eradicates In Vivo Biofilms. Journal of Infectious Diseases, 2014, 210 (9), pp.1357 - 1366. ⟨10.1093/infdis/jiu286⟩. ⟨pasteur-01381819⟩

Collections

PASTEUR ANR
677 View
575 Download

Altmetric

Share

Gmail Facebook X LinkedIn More